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Leonard R. Derogatis - One of the best experts on this subject based on the ideXlab platform.
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the effect of Gepirone er in the treatment of sexual dysfunction in depressed men
The Journal of Sexual Medicine, 2012Co-Authors: Louis F. Fabre, Louis C. Smith, Anita H. Clayton, Irwin Goldstein, Leonard R. DerogatisAbstract:ABSTRACT Introduction Sexual dysfunction is common in patients with major depressive disorder (MDD). Antidepressant medications especially the selective serotonin reuptake inhibitors (SSRIs) may improve depressive symptoms but further decrease sexual function. Gepirone extended release (Gepirone‐ER) differs from the SSRIs in only affecting the 5‐HT 1A receptor and has demonstrated efficacy in treatment of depression and sexual dysfunction in depressed women. This report describes the effect of Gepirone‐ER on sexual function in depressed men. Aim The aims of this article were to study the effects of Gepirone‐ER on sexual function in men with MDD and to determine if positive effects are independent of antidepressant or anxiolytic activity. Main Outcome Measures The main outcome measures of this article were Hamilton depression rating scale (HAMD‐17), and changes in sexual functioning questionnaire (CSFQ). Methods In an 8‐week study, Gepirone‐ER, placebo, or fluoxetine were administered in a double‐blind fashion to 181 depressed men. The CSFQ results were used to determine quality of sexual function. To test for an antidepressant or anxiolytic effect, a 50% reduction in HAMD‐17 score separated antidepressant responders from nonresponders, and item 12 of the HAMD scale (psychic anxiety) scores of 0 or 1 separated anxiolytic responders from nonresponders. Results Gepirone‐ER treatment improved total sexual function compared with placebo measured by the CSFQ at weeks 4 ( P = 0.012) and 8 ( P = 0.046). At 4 weeks, almost every CSFQ domain is improved. The orgasm domain was especially improved, 67% by week 4. Gepirone‐ER antidepressant and anxiolytic nonresponders showed significant improvement in sexual function. Fluoxetine treatment did not produce improvement. In fact, fluoxetine‐treated subjects had lower scores on the total CSFQ, less than placebo, and significantly less than Gepirone‐ER. Conclusion Gepirone‐ER improves sexual dysfunction in depressed men. All domains of sexual function improved. Gepirone‐ER has a pro‐sexual effect independent of antidepressant or anxiolytic activity. Fabre LF, Clayton AH, Smith LC, Goldstein I, and Derogatis LR. The effect of Gepirone‐ER in the treatment of sexual dysfunction in depressed men. J Sex Med 2012;9:821–829.
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The Effect of Gepirone‐ER in the Treatment of Sexual Dysfunction in Depressed Men
The journal of sexual medicine, 2012Co-Authors: Louis F. Fabre, Louis C. Smith, Anita H. Clayton, Irwin Goldstein, Leonard R. DerogatisAbstract:ABSTRACT Introduction Sexual dysfunction is common in patients with major depressive disorder (MDD). Antidepressant medications especially the selective serotonin reuptake inhibitors (SSRIs) may improve depressive symptoms but further decrease sexual function. Gepirone extended release (Gepirone‐ER) differs from the SSRIs in only affecting the 5‐HT 1A receptor and has demonstrated efficacy in treatment of depression and sexual dysfunction in depressed women. This report describes the effect of Gepirone‐ER on sexual function in depressed men. Aim The aims of this article were to study the effects of Gepirone‐ER on sexual function in men with MDD and to determine if positive effects are independent of antidepressant or anxiolytic activity. Main Outcome Measures The main outcome measures of this article were Hamilton depression rating scale (HAMD‐17), and changes in sexual functioning questionnaire (CSFQ). Methods In an 8‐week study, Gepirone‐ER, placebo, or fluoxetine were administered in a double‐blind fashion to 181 depressed men. The CSFQ results were used to determine quality of sexual function. To test for an antidepressant or anxiolytic effect, a 50% reduction in HAMD‐17 score separated antidepressant responders from nonresponders, and item 12 of the HAMD scale (psychic anxiety) scores of 0 or 1 separated anxiolytic responders from nonresponders. Results Gepirone‐ER treatment improved total sexual function compared with placebo measured by the CSFQ at weeks 4 ( P = 0.012) and 8 ( P = 0.046). At 4 weeks, almost every CSFQ domain is improved. The orgasm domain was especially improved, 67% by week 4. Gepirone‐ER antidepressant and anxiolytic nonresponders showed significant improvement in sexual function. Fluoxetine treatment did not produce improvement. In fact, fluoxetine‐treated subjects had lower scores on the total CSFQ, less than placebo, and significantly less than Gepirone‐ER. Conclusion Gepirone‐ER improves sexual dysfunction in depressed men. All domains of sexual function improved. Gepirone‐ER has a pro‐sexual effect independent of antidepressant or anxiolytic activity. Fabre LF, Clayton AH, Smith LC, Goldstein I, and Derogatis LR. The effect of Gepirone‐ER in the treatment of sexual dysfunction in depressed men. J Sex Med 2012;9:821–829.
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Gepirone er treatment of low sexual desire associated with depression in women as measured by the derogatis inventory of sexual function disf fantasy cognition desire domain a post hoc analysis
The Journal of Sexual Medicine, 2011Co-Authors: Louis F. Fabre, Louis C. Smith, Leonard R. DerogatisAbstract:ABSTRACT Introduction Gepirone‐extended release (ER) is effective in treating hypoactive sexual desire disorder (HSDD), as measured by the percent of females with HSDD that no longer met criteria for HSDD treatment. Another approach is to determine treatment effect on sexual desire using a recognized rating scale for sexual function. Because Gepirone‐ER has antidepressant and anxiolytic effects, investigation of these effects on sexual desire is appropriate. Aim The aim of this study was to determine whether Gepirone‐ER has positive effects on sexual desire as measured by the DeRogatis Inventory of Sexual Function (DISF) in a post hoc analysis of 8‐ and 24‐week studies and if this Gepirone effect is independent of its antidepressant or anxiolytic activity. Main Outcome Measures The main outcome measures used for this study were the Hamilton Depression Rating Scale (HAMD‐25), change from baseline (CFB), and DISF CFB. Methods: Three hundred thirty‐four women selected for depressive symptoms, not sexual dysfunction, received Gepirone‐ER (40–80 mg/day) in a controlled study of atypical depression using the HAMD‐25 to measure antidepressant efficacy and a DISF subscale (domain I) to measure sexual cognition/fantasy (desire). After treatment, a 50% reduction from baseline HAMD‐25 score identified antidepressant responders. Item 12 of HAMD scale (psychic anxiety) was used to define anxiolytic response scores of 0, 1 as responders, and scores of 2, 3, and 4 as nonresponders. Results: Gepirone‐ER had no significant antidepressant or an anxiolytic effect in study 134006; however, DISF results demonstrate that Gepirone‐ER improves sexual desire in short term ( P = 0.043) and long term ( P = 0.006). Both Gepirone‐ER antidepressant and anxiolytic responders have statistically significant improved sexual desire. Gepirone‐ER antidepressant and anxiolytic nonresponders also show statistically significant improvement. Conclusions In depressed women, Gepirone‐ER has three mechanisms of action affecting sexual desire: an antidepressant effect, an anxiolytic effect, and a pro‐sexual effect. Gepirone‐ER improves sexual desire from the 24th to the 50th percentile according to population norms for the DISF. Fabre LF, Smith LC, and DeRogatis LR. Gepirone‐ER treatment of low sexual desire associated with depression in women as measured by the DeRogatis inventory of sexual function (DISF) fantasy/cognition (desire) domain—A post Hoc analysis. J Sex Med 2011;8:2569–2581.
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Gepirone‐ER Treatment of Low Sexual Desire Associated with Depression in Women as Measured by the DeRogatis Inventory of Sexual Function (DISF) Fantasy/Cognition (Desire) Domain—A Post Hoc Analysis
The journal of sexual medicine, 2011Co-Authors: Louis F. Fabre, Louis C. Smith, Leonard R. DerogatisAbstract:ABSTRACT Introduction Gepirone‐extended release (ER) is effective in treating hypoactive sexual desire disorder (HSDD), as measured by the percent of females with HSDD that no longer met criteria for HSDD treatment. Another approach is to determine treatment effect on sexual desire using a recognized rating scale for sexual function. Because Gepirone‐ER has antidepressant and anxiolytic effects, investigation of these effects on sexual desire is appropriate. Aim The aim of this study was to determine whether Gepirone‐ER has positive effects on sexual desire as measured by the DeRogatis Inventory of Sexual Function (DISF) in a post hoc analysis of 8‐ and 24‐week studies and if this Gepirone effect is independent of its antidepressant or anxiolytic activity. Main Outcome Measures The main outcome measures used for this study were the Hamilton Depression Rating Scale (HAMD‐25), change from baseline (CFB), and DISF CFB. Methods: Three hundred thirty‐four women selected for depressive symptoms, not sexual dysfunction, received Gepirone‐ER (40–80 mg/day) in a controlled study of atypical depression using the HAMD‐25 to measure antidepressant efficacy and a DISF subscale (domain I) to measure sexual cognition/fantasy (desire). After treatment, a 50% reduction from baseline HAMD‐25 score identified antidepressant responders. Item 12 of HAMD scale (psychic anxiety) was used to define anxiolytic response scores of 0, 1 as responders, and scores of 2, 3, and 4 as nonresponders. Results: Gepirone‐ER had no significant antidepressant or an anxiolytic effect in study 134006; however, DISF results demonstrate that Gepirone‐ER improves sexual desire in short term ( P = 0.043) and long term ( P = 0.006). Both Gepirone‐ER antidepressant and anxiolytic responders have statistically significant improved sexual desire. Gepirone‐ER antidepressant and anxiolytic nonresponders also show statistically significant improvement. Conclusions In depressed women, Gepirone‐ER has three mechanisms of action affecting sexual desire: an antidepressant effect, an anxiolytic effect, and a pro‐sexual effect. Gepirone‐ER improves sexual desire from the 24th to the 50th percentile according to population norms for the DISF. Fabre LF, Smith LC, and DeRogatis LR. Gepirone‐ER treatment of low sexual desire associated with depression in women as measured by the DeRogatis inventory of sexual function (DISF) fantasy/cognition (desire) domain—A post Hoc analysis. J Sex Med 2011;8:2569–2581.
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Gepirone-ER Treatment of Hypoactive Sexual Desire Disorder (HSDD) Associated with Depression in Women
The journal of sexual medicine, 2011Co-Authors: Louis F. Fabre, Louis C. Smith, Candace S. Brown, Leonard R. DerogatisAbstract:ABSTRACT Introduction There is currently no Food and Drug Administration (FDA)-approved treatment for hypoactive sexual desire disorder (HSDD). FDA approval of products utilizing testosterone has been delayed due to possible safety concerns. Flibanserin, a 5-HT 1A agonist, 5-HT 2 antagonist, and Gepirone-ER, a 5-HT 1A agonist, have been shown to have activity in treatment of HSDD. However, more recently, the FDA issued a non-approval letter for flibanserin. Aim To study the effect of Gepirone-ER on HSDD in women with major depressive disorder (MDD). Methods At baseline and post-treatment visits, a trained psychiatrist made diagnoses of HSDD based on Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria. Subjects meeting criteria for HSDD were followed to observe the effect of Gepirone-ER (20–80 mg/day), comparator antidepressants (fluoxetine, 20–40 mg/day or paroxetine, 10–40 mg/day), or placebo in reversing DSM-IV diagnosis. A subpopulation of women with Hamilton Depression Rating Scale (HAMD-17) entry scores of 18 or less was evaluated. Adverse events (AEs) of sexual dysfunction were also collected. Main Outcome Measure Number (%) of patients who no longer met criteria for HSDD (percent resolved). Results Eight hundred seventy-five women (18–64 years of age, average 38 years old, ∼80% premenopausal) entered three studies; 668 (72.5%) completed. Only 161 (18.4%) met DSM-IV criteria for HSDD. Cumulatively, 63% of Gepirone-ER-treated patients reversed their diagnosis of HSDD compared to 40% of placebo-treated patients at end point (8 weeks) ( P = 0.007). Selective serotonin reuptake inhibitor-treated patients were not different from placebo. Significant results for Gepirone-ER occurred by week 2 ( P = 0.0001). Patients who were mildly depressed (HAMD scores of 18 or less) also improved at week 2 ( P = 0.01) and week 8 ( P = 0.07). Sexual dysfunction AEs were significantly less in Gepirone-ER-treated patients than placebo ( P = 0.013). Conclusions Gepirone-ER may have efficacy in the treatment of HSDD among depressed and possibly nondepressed women. Efficacy occurs by week 2, and does not seem to be purely an antidepressant effect. Fabre LF, Brown CS, Smith LC, and DeRogatis LR. Gepirone-ER treatment of hypoactive sexual desire disorder (HSDD) associated with depression in women.
Louis F. Fabre - One of the best experts on this subject based on the ideXlab platform.
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the effect of Gepirone er in the treatment of sexual dysfunction in depressed men
The Journal of Sexual Medicine, 2012Co-Authors: Louis F. Fabre, Louis C. Smith, Anita H. Clayton, Irwin Goldstein, Leonard R. DerogatisAbstract:ABSTRACT Introduction Sexual dysfunction is common in patients with major depressive disorder (MDD). Antidepressant medications especially the selective serotonin reuptake inhibitors (SSRIs) may improve depressive symptoms but further decrease sexual function. Gepirone extended release (Gepirone‐ER) differs from the SSRIs in only affecting the 5‐HT 1A receptor and has demonstrated efficacy in treatment of depression and sexual dysfunction in depressed women. This report describes the effect of Gepirone‐ER on sexual function in depressed men. Aim The aims of this article were to study the effects of Gepirone‐ER on sexual function in men with MDD and to determine if positive effects are independent of antidepressant or anxiolytic activity. Main Outcome Measures The main outcome measures of this article were Hamilton depression rating scale (HAMD‐17), and changes in sexual functioning questionnaire (CSFQ). Methods In an 8‐week study, Gepirone‐ER, placebo, or fluoxetine were administered in a double‐blind fashion to 181 depressed men. The CSFQ results were used to determine quality of sexual function. To test for an antidepressant or anxiolytic effect, a 50% reduction in HAMD‐17 score separated antidepressant responders from nonresponders, and item 12 of the HAMD scale (psychic anxiety) scores of 0 or 1 separated anxiolytic responders from nonresponders. Results Gepirone‐ER treatment improved total sexual function compared with placebo measured by the CSFQ at weeks 4 ( P = 0.012) and 8 ( P = 0.046). At 4 weeks, almost every CSFQ domain is improved. The orgasm domain was especially improved, 67% by week 4. Gepirone‐ER antidepressant and anxiolytic nonresponders showed significant improvement in sexual function. Fluoxetine treatment did not produce improvement. In fact, fluoxetine‐treated subjects had lower scores on the total CSFQ, less than placebo, and significantly less than Gepirone‐ER. Conclusion Gepirone‐ER improves sexual dysfunction in depressed men. All domains of sexual function improved. Gepirone‐ER has a pro‐sexual effect independent of antidepressant or anxiolytic activity. Fabre LF, Clayton AH, Smith LC, Goldstein I, and Derogatis LR. The effect of Gepirone‐ER in the treatment of sexual dysfunction in depressed men. J Sex Med 2012;9:821–829.
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The Effect of Gepirone‐ER in the Treatment of Sexual Dysfunction in Depressed Men
The journal of sexual medicine, 2012Co-Authors: Louis F. Fabre, Louis C. Smith, Anita H. Clayton, Irwin Goldstein, Leonard R. DerogatisAbstract:ABSTRACT Introduction Sexual dysfunction is common in patients with major depressive disorder (MDD). Antidepressant medications especially the selective serotonin reuptake inhibitors (SSRIs) may improve depressive symptoms but further decrease sexual function. Gepirone extended release (Gepirone‐ER) differs from the SSRIs in only affecting the 5‐HT 1A receptor and has demonstrated efficacy in treatment of depression and sexual dysfunction in depressed women. This report describes the effect of Gepirone‐ER on sexual function in depressed men. Aim The aims of this article were to study the effects of Gepirone‐ER on sexual function in men with MDD and to determine if positive effects are independent of antidepressant or anxiolytic activity. Main Outcome Measures The main outcome measures of this article were Hamilton depression rating scale (HAMD‐17), and changes in sexual functioning questionnaire (CSFQ). Methods In an 8‐week study, Gepirone‐ER, placebo, or fluoxetine were administered in a double‐blind fashion to 181 depressed men. The CSFQ results were used to determine quality of sexual function. To test for an antidepressant or anxiolytic effect, a 50% reduction in HAMD‐17 score separated antidepressant responders from nonresponders, and item 12 of the HAMD scale (psychic anxiety) scores of 0 or 1 separated anxiolytic responders from nonresponders. Results Gepirone‐ER treatment improved total sexual function compared with placebo measured by the CSFQ at weeks 4 ( P = 0.012) and 8 ( P = 0.046). At 4 weeks, almost every CSFQ domain is improved. The orgasm domain was especially improved, 67% by week 4. Gepirone‐ER antidepressant and anxiolytic nonresponders showed significant improvement in sexual function. Fluoxetine treatment did not produce improvement. In fact, fluoxetine‐treated subjects had lower scores on the total CSFQ, less than placebo, and significantly less than Gepirone‐ER. Conclusion Gepirone‐ER improves sexual dysfunction in depressed men. All domains of sexual function improved. Gepirone‐ER has a pro‐sexual effect independent of antidepressant or anxiolytic activity. Fabre LF, Clayton AH, Smith LC, Goldstein I, and Derogatis LR. The effect of Gepirone‐ER in the treatment of sexual dysfunction in depressed men. J Sex Med 2012;9:821–829.
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Gepirone er treatment of low sexual desire associated with depression in women as measured by the derogatis inventory of sexual function disf fantasy cognition desire domain a post hoc analysis
The Journal of Sexual Medicine, 2011Co-Authors: Louis F. Fabre, Louis C. Smith, Leonard R. DerogatisAbstract:ABSTRACT Introduction Gepirone‐extended release (ER) is effective in treating hypoactive sexual desire disorder (HSDD), as measured by the percent of females with HSDD that no longer met criteria for HSDD treatment. Another approach is to determine treatment effect on sexual desire using a recognized rating scale for sexual function. Because Gepirone‐ER has antidepressant and anxiolytic effects, investigation of these effects on sexual desire is appropriate. Aim The aim of this study was to determine whether Gepirone‐ER has positive effects on sexual desire as measured by the DeRogatis Inventory of Sexual Function (DISF) in a post hoc analysis of 8‐ and 24‐week studies and if this Gepirone effect is independent of its antidepressant or anxiolytic activity. Main Outcome Measures The main outcome measures used for this study were the Hamilton Depression Rating Scale (HAMD‐25), change from baseline (CFB), and DISF CFB. Methods: Three hundred thirty‐four women selected for depressive symptoms, not sexual dysfunction, received Gepirone‐ER (40–80 mg/day) in a controlled study of atypical depression using the HAMD‐25 to measure antidepressant efficacy and a DISF subscale (domain I) to measure sexual cognition/fantasy (desire). After treatment, a 50% reduction from baseline HAMD‐25 score identified antidepressant responders. Item 12 of HAMD scale (psychic anxiety) was used to define anxiolytic response scores of 0, 1 as responders, and scores of 2, 3, and 4 as nonresponders. Results: Gepirone‐ER had no significant antidepressant or an anxiolytic effect in study 134006; however, DISF results demonstrate that Gepirone‐ER improves sexual desire in short term ( P = 0.043) and long term ( P = 0.006). Both Gepirone‐ER antidepressant and anxiolytic responders have statistically significant improved sexual desire. Gepirone‐ER antidepressant and anxiolytic nonresponders also show statistically significant improvement. Conclusions In depressed women, Gepirone‐ER has three mechanisms of action affecting sexual desire: an antidepressant effect, an anxiolytic effect, and a pro‐sexual effect. Gepirone‐ER improves sexual desire from the 24th to the 50th percentile according to population norms for the DISF. Fabre LF, Smith LC, and DeRogatis LR. Gepirone‐ER treatment of low sexual desire associated with depression in women as measured by the DeRogatis inventory of sexual function (DISF) fantasy/cognition (desire) domain—A post Hoc analysis. J Sex Med 2011;8:2569–2581.
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Gepirone‐ER Treatment of Low Sexual Desire Associated with Depression in Women as Measured by the DeRogatis Inventory of Sexual Function (DISF) Fantasy/Cognition (Desire) Domain—A Post Hoc Analysis
The journal of sexual medicine, 2011Co-Authors: Louis F. Fabre, Louis C. Smith, Leonard R. DerogatisAbstract:ABSTRACT Introduction Gepirone‐extended release (ER) is effective in treating hypoactive sexual desire disorder (HSDD), as measured by the percent of females with HSDD that no longer met criteria for HSDD treatment. Another approach is to determine treatment effect on sexual desire using a recognized rating scale for sexual function. Because Gepirone‐ER has antidepressant and anxiolytic effects, investigation of these effects on sexual desire is appropriate. Aim The aim of this study was to determine whether Gepirone‐ER has positive effects on sexual desire as measured by the DeRogatis Inventory of Sexual Function (DISF) in a post hoc analysis of 8‐ and 24‐week studies and if this Gepirone effect is independent of its antidepressant or anxiolytic activity. Main Outcome Measures The main outcome measures used for this study were the Hamilton Depression Rating Scale (HAMD‐25), change from baseline (CFB), and DISF CFB. Methods: Three hundred thirty‐four women selected for depressive symptoms, not sexual dysfunction, received Gepirone‐ER (40–80 mg/day) in a controlled study of atypical depression using the HAMD‐25 to measure antidepressant efficacy and a DISF subscale (domain I) to measure sexual cognition/fantasy (desire). After treatment, a 50% reduction from baseline HAMD‐25 score identified antidepressant responders. Item 12 of HAMD scale (psychic anxiety) was used to define anxiolytic response scores of 0, 1 as responders, and scores of 2, 3, and 4 as nonresponders. Results: Gepirone‐ER had no significant antidepressant or an anxiolytic effect in study 134006; however, DISF results demonstrate that Gepirone‐ER improves sexual desire in short term ( P = 0.043) and long term ( P = 0.006). Both Gepirone‐ER antidepressant and anxiolytic responders have statistically significant improved sexual desire. Gepirone‐ER antidepressant and anxiolytic nonresponders also show statistically significant improvement. Conclusions In depressed women, Gepirone‐ER has three mechanisms of action affecting sexual desire: an antidepressant effect, an anxiolytic effect, and a pro‐sexual effect. Gepirone‐ER improves sexual desire from the 24th to the 50th percentile according to population norms for the DISF. Fabre LF, Smith LC, and DeRogatis LR. Gepirone‐ER treatment of low sexual desire associated with depression in women as measured by the DeRogatis inventory of sexual function (DISF) fantasy/cognition (desire) domain—A post Hoc analysis. J Sex Med 2011;8:2569–2581.
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Gepirone-ER Treatment of Hypoactive Sexual Desire Disorder (HSDD) Associated with Depression in Women
The journal of sexual medicine, 2011Co-Authors: Louis F. Fabre, Louis C. Smith, Candace S. Brown, Leonard R. DerogatisAbstract:ABSTRACT Introduction There is currently no Food and Drug Administration (FDA)-approved treatment for hypoactive sexual desire disorder (HSDD). FDA approval of products utilizing testosterone has been delayed due to possible safety concerns. Flibanserin, a 5-HT 1A agonist, 5-HT 2 antagonist, and Gepirone-ER, a 5-HT 1A agonist, have been shown to have activity in treatment of HSDD. However, more recently, the FDA issued a non-approval letter for flibanserin. Aim To study the effect of Gepirone-ER on HSDD in women with major depressive disorder (MDD). Methods At baseline and post-treatment visits, a trained psychiatrist made diagnoses of HSDD based on Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria. Subjects meeting criteria for HSDD were followed to observe the effect of Gepirone-ER (20–80 mg/day), comparator antidepressants (fluoxetine, 20–40 mg/day or paroxetine, 10–40 mg/day), or placebo in reversing DSM-IV diagnosis. A subpopulation of women with Hamilton Depression Rating Scale (HAMD-17) entry scores of 18 or less was evaluated. Adverse events (AEs) of sexual dysfunction were also collected. Main Outcome Measure Number (%) of patients who no longer met criteria for HSDD (percent resolved). Results Eight hundred seventy-five women (18–64 years of age, average 38 years old, ∼80% premenopausal) entered three studies; 668 (72.5%) completed. Only 161 (18.4%) met DSM-IV criteria for HSDD. Cumulatively, 63% of Gepirone-ER-treated patients reversed their diagnosis of HSDD compared to 40% of placebo-treated patients at end point (8 weeks) ( P = 0.007). Selective serotonin reuptake inhibitor-treated patients were not different from placebo. Significant results for Gepirone-ER occurred by week 2 ( P = 0.0001). Patients who were mildly depressed (HAMD scores of 18 or less) also improved at week 2 ( P = 0.01) and week 8 ( P = 0.07). Sexual dysfunction AEs were significantly less in Gepirone-ER-treated patients than placebo ( P = 0.013). Conclusions Gepirone-ER may have efficacy in the treatment of HSDD among depressed and possibly nondepressed women. Efficacy occurs by week 2, and does not seem to be purely an antidepressant effect. Fabre LF, Brown CS, Smith LC, and DeRogatis LR. Gepirone-ER treatment of hypoactive sexual desire disorder (HSDD) associated with depression in women.
Louis C. Smith - One of the best experts on this subject based on the ideXlab platform.
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the effect of Gepirone er in the treatment of sexual dysfunction in depressed men
The Journal of Sexual Medicine, 2012Co-Authors: Louis F. Fabre, Louis C. Smith, Anita H. Clayton, Irwin Goldstein, Leonard R. DerogatisAbstract:ABSTRACT Introduction Sexual dysfunction is common in patients with major depressive disorder (MDD). Antidepressant medications especially the selective serotonin reuptake inhibitors (SSRIs) may improve depressive symptoms but further decrease sexual function. Gepirone extended release (Gepirone‐ER) differs from the SSRIs in only affecting the 5‐HT 1A receptor and has demonstrated efficacy in treatment of depression and sexual dysfunction in depressed women. This report describes the effect of Gepirone‐ER on sexual function in depressed men. Aim The aims of this article were to study the effects of Gepirone‐ER on sexual function in men with MDD and to determine if positive effects are independent of antidepressant or anxiolytic activity. Main Outcome Measures The main outcome measures of this article were Hamilton depression rating scale (HAMD‐17), and changes in sexual functioning questionnaire (CSFQ). Methods In an 8‐week study, Gepirone‐ER, placebo, or fluoxetine were administered in a double‐blind fashion to 181 depressed men. The CSFQ results were used to determine quality of sexual function. To test for an antidepressant or anxiolytic effect, a 50% reduction in HAMD‐17 score separated antidepressant responders from nonresponders, and item 12 of the HAMD scale (psychic anxiety) scores of 0 or 1 separated anxiolytic responders from nonresponders. Results Gepirone‐ER treatment improved total sexual function compared with placebo measured by the CSFQ at weeks 4 ( P = 0.012) and 8 ( P = 0.046). At 4 weeks, almost every CSFQ domain is improved. The orgasm domain was especially improved, 67% by week 4. Gepirone‐ER antidepressant and anxiolytic nonresponders showed significant improvement in sexual function. Fluoxetine treatment did not produce improvement. In fact, fluoxetine‐treated subjects had lower scores on the total CSFQ, less than placebo, and significantly less than Gepirone‐ER. Conclusion Gepirone‐ER improves sexual dysfunction in depressed men. All domains of sexual function improved. Gepirone‐ER has a pro‐sexual effect independent of antidepressant or anxiolytic activity. Fabre LF, Clayton AH, Smith LC, Goldstein I, and Derogatis LR. The effect of Gepirone‐ER in the treatment of sexual dysfunction in depressed men. J Sex Med 2012;9:821–829.
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The Effect of Gepirone‐ER in the Treatment of Sexual Dysfunction in Depressed Men
The journal of sexual medicine, 2012Co-Authors: Louis F. Fabre, Louis C. Smith, Anita H. Clayton, Irwin Goldstein, Leonard R. DerogatisAbstract:ABSTRACT Introduction Sexual dysfunction is common in patients with major depressive disorder (MDD). Antidepressant medications especially the selective serotonin reuptake inhibitors (SSRIs) may improve depressive symptoms but further decrease sexual function. Gepirone extended release (Gepirone‐ER) differs from the SSRIs in only affecting the 5‐HT 1A receptor and has demonstrated efficacy in treatment of depression and sexual dysfunction in depressed women. This report describes the effect of Gepirone‐ER on sexual function in depressed men. Aim The aims of this article were to study the effects of Gepirone‐ER on sexual function in men with MDD and to determine if positive effects are independent of antidepressant or anxiolytic activity. Main Outcome Measures The main outcome measures of this article were Hamilton depression rating scale (HAMD‐17), and changes in sexual functioning questionnaire (CSFQ). Methods In an 8‐week study, Gepirone‐ER, placebo, or fluoxetine were administered in a double‐blind fashion to 181 depressed men. The CSFQ results were used to determine quality of sexual function. To test for an antidepressant or anxiolytic effect, a 50% reduction in HAMD‐17 score separated antidepressant responders from nonresponders, and item 12 of the HAMD scale (psychic anxiety) scores of 0 or 1 separated anxiolytic responders from nonresponders. Results Gepirone‐ER treatment improved total sexual function compared with placebo measured by the CSFQ at weeks 4 ( P = 0.012) and 8 ( P = 0.046). At 4 weeks, almost every CSFQ domain is improved. The orgasm domain was especially improved, 67% by week 4. Gepirone‐ER antidepressant and anxiolytic nonresponders showed significant improvement in sexual function. Fluoxetine treatment did not produce improvement. In fact, fluoxetine‐treated subjects had lower scores on the total CSFQ, less than placebo, and significantly less than Gepirone‐ER. Conclusion Gepirone‐ER improves sexual dysfunction in depressed men. All domains of sexual function improved. Gepirone‐ER has a pro‐sexual effect independent of antidepressant or anxiolytic activity. Fabre LF, Clayton AH, Smith LC, Goldstein I, and Derogatis LR. The effect of Gepirone‐ER in the treatment of sexual dysfunction in depressed men. J Sex Med 2012;9:821–829.
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Gepirone er treatment of low sexual desire associated with depression in women as measured by the derogatis inventory of sexual function disf fantasy cognition desire domain a post hoc analysis
The Journal of Sexual Medicine, 2011Co-Authors: Louis F. Fabre, Louis C. Smith, Leonard R. DerogatisAbstract:ABSTRACT Introduction Gepirone‐extended release (ER) is effective in treating hypoactive sexual desire disorder (HSDD), as measured by the percent of females with HSDD that no longer met criteria for HSDD treatment. Another approach is to determine treatment effect on sexual desire using a recognized rating scale for sexual function. Because Gepirone‐ER has antidepressant and anxiolytic effects, investigation of these effects on sexual desire is appropriate. Aim The aim of this study was to determine whether Gepirone‐ER has positive effects on sexual desire as measured by the DeRogatis Inventory of Sexual Function (DISF) in a post hoc analysis of 8‐ and 24‐week studies and if this Gepirone effect is independent of its antidepressant or anxiolytic activity. Main Outcome Measures The main outcome measures used for this study were the Hamilton Depression Rating Scale (HAMD‐25), change from baseline (CFB), and DISF CFB. Methods: Three hundred thirty‐four women selected for depressive symptoms, not sexual dysfunction, received Gepirone‐ER (40–80 mg/day) in a controlled study of atypical depression using the HAMD‐25 to measure antidepressant efficacy and a DISF subscale (domain I) to measure sexual cognition/fantasy (desire). After treatment, a 50% reduction from baseline HAMD‐25 score identified antidepressant responders. Item 12 of HAMD scale (psychic anxiety) was used to define anxiolytic response scores of 0, 1 as responders, and scores of 2, 3, and 4 as nonresponders. Results: Gepirone‐ER had no significant antidepressant or an anxiolytic effect in study 134006; however, DISF results demonstrate that Gepirone‐ER improves sexual desire in short term ( P = 0.043) and long term ( P = 0.006). Both Gepirone‐ER antidepressant and anxiolytic responders have statistically significant improved sexual desire. Gepirone‐ER antidepressant and anxiolytic nonresponders also show statistically significant improvement. Conclusions In depressed women, Gepirone‐ER has three mechanisms of action affecting sexual desire: an antidepressant effect, an anxiolytic effect, and a pro‐sexual effect. Gepirone‐ER improves sexual desire from the 24th to the 50th percentile according to population norms for the DISF. Fabre LF, Smith LC, and DeRogatis LR. Gepirone‐ER treatment of low sexual desire associated with depression in women as measured by the DeRogatis inventory of sexual function (DISF) fantasy/cognition (desire) domain—A post Hoc analysis. J Sex Med 2011;8:2569–2581.
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Gepirone‐ER Treatment of Low Sexual Desire Associated with Depression in Women as Measured by the DeRogatis Inventory of Sexual Function (DISF) Fantasy/Cognition (Desire) Domain—A Post Hoc Analysis
The journal of sexual medicine, 2011Co-Authors: Louis F. Fabre, Louis C. Smith, Leonard R. DerogatisAbstract:ABSTRACT Introduction Gepirone‐extended release (ER) is effective in treating hypoactive sexual desire disorder (HSDD), as measured by the percent of females with HSDD that no longer met criteria for HSDD treatment. Another approach is to determine treatment effect on sexual desire using a recognized rating scale for sexual function. Because Gepirone‐ER has antidepressant and anxiolytic effects, investigation of these effects on sexual desire is appropriate. Aim The aim of this study was to determine whether Gepirone‐ER has positive effects on sexual desire as measured by the DeRogatis Inventory of Sexual Function (DISF) in a post hoc analysis of 8‐ and 24‐week studies and if this Gepirone effect is independent of its antidepressant or anxiolytic activity. Main Outcome Measures The main outcome measures used for this study were the Hamilton Depression Rating Scale (HAMD‐25), change from baseline (CFB), and DISF CFB. Methods: Three hundred thirty‐four women selected for depressive symptoms, not sexual dysfunction, received Gepirone‐ER (40–80 mg/day) in a controlled study of atypical depression using the HAMD‐25 to measure antidepressant efficacy and a DISF subscale (domain I) to measure sexual cognition/fantasy (desire). After treatment, a 50% reduction from baseline HAMD‐25 score identified antidepressant responders. Item 12 of HAMD scale (psychic anxiety) was used to define anxiolytic response scores of 0, 1 as responders, and scores of 2, 3, and 4 as nonresponders. Results: Gepirone‐ER had no significant antidepressant or an anxiolytic effect in study 134006; however, DISF results demonstrate that Gepirone‐ER improves sexual desire in short term ( P = 0.043) and long term ( P = 0.006). Both Gepirone‐ER antidepressant and anxiolytic responders have statistically significant improved sexual desire. Gepirone‐ER antidepressant and anxiolytic nonresponders also show statistically significant improvement. Conclusions In depressed women, Gepirone‐ER has three mechanisms of action affecting sexual desire: an antidepressant effect, an anxiolytic effect, and a pro‐sexual effect. Gepirone‐ER improves sexual desire from the 24th to the 50th percentile according to population norms for the DISF. Fabre LF, Smith LC, and DeRogatis LR. Gepirone‐ER treatment of low sexual desire associated with depression in women as measured by the DeRogatis inventory of sexual function (DISF) fantasy/cognition (desire) domain—A post Hoc analysis. J Sex Med 2011;8:2569–2581.
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Gepirone-ER Treatment of Hypoactive Sexual Desire Disorder (HSDD) Associated with Depression in Women
The journal of sexual medicine, 2011Co-Authors: Louis F. Fabre, Louis C. Smith, Candace S. Brown, Leonard R. DerogatisAbstract:ABSTRACT Introduction There is currently no Food and Drug Administration (FDA)-approved treatment for hypoactive sexual desire disorder (HSDD). FDA approval of products utilizing testosterone has been delayed due to possible safety concerns. Flibanserin, a 5-HT 1A agonist, 5-HT 2 antagonist, and Gepirone-ER, a 5-HT 1A agonist, have been shown to have activity in treatment of HSDD. However, more recently, the FDA issued a non-approval letter for flibanserin. Aim To study the effect of Gepirone-ER on HSDD in women with major depressive disorder (MDD). Methods At baseline and post-treatment visits, a trained psychiatrist made diagnoses of HSDD based on Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria. Subjects meeting criteria for HSDD were followed to observe the effect of Gepirone-ER (20–80 mg/day), comparator antidepressants (fluoxetine, 20–40 mg/day or paroxetine, 10–40 mg/day), or placebo in reversing DSM-IV diagnosis. A subpopulation of women with Hamilton Depression Rating Scale (HAMD-17) entry scores of 18 or less was evaluated. Adverse events (AEs) of sexual dysfunction were also collected. Main Outcome Measure Number (%) of patients who no longer met criteria for HSDD (percent resolved). Results Eight hundred seventy-five women (18–64 years of age, average 38 years old, ∼80% premenopausal) entered three studies; 668 (72.5%) completed. Only 161 (18.4%) met DSM-IV criteria for HSDD. Cumulatively, 63% of Gepirone-ER-treated patients reversed their diagnosis of HSDD compared to 40% of placebo-treated patients at end point (8 weeks) ( P = 0.007). Selective serotonin reuptake inhibitor-treated patients were not different from placebo. Significant results for Gepirone-ER occurred by week 2 ( P = 0.0001). Patients who were mildly depressed (HAMD scores of 18 or less) also improved at week 2 ( P = 0.01) and week 8 ( P = 0.07). Sexual dysfunction AEs were significantly less in Gepirone-ER-treated patients than placebo ( P = 0.013). Conclusions Gepirone-ER may have efficacy in the treatment of HSDD among depressed and possibly nondepressed women. Efficacy occurs by week 2, and does not seem to be purely an antidepressant effect. Fabre LF, Brown CS, Smith LC, and DeRogatis LR. Gepirone-ER treatment of hypoactive sexual desire disorder (HSDD) associated with depression in women.
Klaus A. Miczek - One of the best experts on this subject based on the ideXlab platform.
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Alcohol, anxiolytics and social stress in rats
Psychopharmacology, 1995Co-Authors: Walter Tornatzky, Klaus A. MiczekAbstract:The main objective was to compare the anxiolytic-like profiles of alcohol, diazepam and Gepirone along the stress intensity gradient which characterizes consecutive phases of a social confrontation. The acute social stress situation consisted of initially placing the experimental rat as an intruder into the homecage of a resident while the resident was not present, termed the “anticipatory” phase, thereafter permitting brief physical agonistic interactions with the re-introduced resident until the intruder was forced into a submissive supine posture and emitted ultrasonic vocalizations (USV), and eventually exposing the intruder to the resident's threats for 1 h, while being shielded from potential injurious attacks. The hyperthermia, measured via telemetry, in the “anticipatory” phase prior to defeat and in reaction to threats, was decreased by alcohol, Gepirone and diazepam; alcohol and Gepirone were also effective in attenuating “anticipatory” tachycardia. Alcohol, like Gepirone and diazepam, also decreased defensive responses and ultrasonic vocalizations in the “anticipatory” phase of the confrontation, but none of these drugs affected defensive reactions to threats which immediately followed defeat. Gepirone had no systematic sedative effects throughout the confrontation; infact, it dose-dependently reduced the stress-induced suppression of locomotor activity during the “anticipatory” phase. In contrast, at higher doses, alcohol as well as diazepam had marked sedative effects as evidenced by several behavioral parameters (i.e. lie, crouch, walk). The anxiolytic-like profile of hyperthermia, tachycardia, USV and defensive behavior in the “anticipatory” phase of the confrontation by alcohol, Gepirone and diazepam contrasted with the lack thereof during the more intense reactive phase. This differential pattern of effects appears to be relevant to the clinical distinctions between anticipatory anxiety and other affective disturbances.
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Diazepam withdrawal: effects of diazepam and Gepirone on acoustic startle-induced 22 kHz ultrasonic vocalizations.
Psychopharmacology, 1994Co-Authors: J. A. Vivian, William J. Farrell, Scott B. Sapperstein, Klaus A. MiczekAbstract:It has proven difficult to demonstrate and study the “anxiogenic” quality of drug withdrawal states in animals. Ultrasonic vocalizations (USV) in response to acoustic startle stimuli have shown promise as a measure of affect and may represent “distress” responses during diazepam withdrawal. Three experiments evaluated the association between USV and “distress” by comparing the effects of diazepam as a prototypic benzodiazepine agonist and the putative anxiolytic Gepirone with affinity for 5-hydroxytryptamine (5-HT1A) receptors in naive and diazepam-withdrawn subjects. Adult male Long-Evans rats were exposed to acoustic startle sessions consisting of nine 105 dB and nine 115 dB stimuli. USV at 20–30 kHz were readily emitted during startle and often commenced after the third or fourth stimulus presentation. Acutely, intraperitoneal (IP) administration of diazepam (0.1–3 mg/kg) and Gepirone (0.1–1 mg/kg) decreased USV dose-dependently without affecting the startle reflex; Gepirone also decreased tail flick latency. Startle-induced USV were also sensitive to the “anxiogenic” effects of withdrawal from diazepam exposure (0, 2.5, 5, 10 mg/kg b.i.d. IP×5 days). Twenty-four hours after the last diazepam injection, rats were hyperreactive to startle stimuli and doubled their rate of USV over vehicle-treated controls. Gepirone (0.1–1 mg/kg IP), but not diazepam (3–20 mg/kg IP) antagonized the increased rate of USV in rats withdrawn from 10 mg/kg b.i.d. diazepam. Diazepam (2.5–10 mg/kg IP) antagonized the increased rate of USV in rats withdrawn from 2.5 mg/kg b.i.d. diazepam. USV induced by acoustic startle stimuli are sensitive to the anxiolytic effects of benzodiazepine and 5-HT1A receptor agonists and permit the assessment of the “anxiogenic” properties of diazepam withdrawal. The potent effect of Gepirone on USV suggests a serotonergic amelioration of the “anxiogenic” aspects of diazepam withdrawal.
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Diazepam and Gepirone selectively attenuate either 20–32 or 32–64 kHz ultrasonic vocalizations during aggressive encounters
Psychopharmacology, 1993Co-Authors: J. A. Vivian, Klaus A. MiczekAbstract:Ultrasonic vocalizations (USV) in rats may communicate “affective” states, as they occur only in highly significant behavioral contexts such as during sex, aggression, exposure to painful or startling events. This proposal was evaluated in an experiment with adult male Long-Evans rats during agonistic encounters; specifically, the effects of diazepam, flumazenil and Gepirone were studied on different types of USV emitted by intruder rats exposed to resident attacks and to “threat of attacks” (i.e., intruder protected within the home cage of the resident by a wire mesh cage). USV were readily emitted during agonistic encounters and consisted primarily of two distributions of pure tone whistles: 0.3- to 3-s, 20- to 32-kHz (“low”) signals and 0.02- to 0.3-s, 32- to 64-kHz (“high”) signals. A considerable repertoire of frequency modulated signals was observed and proved to be sensitive to the anxiolytic treatments. Diazepam (1–6 mg/kg) dose-dependently decreased high frequency USV during the threat of attack and decreased the mean pitch of the most predominant vocalizations but did not affect low frequency USV or the audible squeals (AS) in response to bites. Gepirone (0.3–6 mg/kg) dose-dependently decreased low frequency USV and did not affect high frequency USV or AS. Responses to thermal pain stimuli remained unaltered by all drugs, while walking duration was decreased and crouch postures were increased after diazepam but not after Gepirone administration. Gepirone in the present dose range had minimal effects on submissive, exploratory and locomotor behaviors. The pattern of results is consistent with the proposal that low frequency USV reflect a heightened affective state which is ameliorated with 5HT1A but not benzodiazepine anxiolytics, and suggests that the suppression of high frequency USV in reaction to attacks or threats coincides with the sedative or muscle relaxant properties of these compounds.
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diazepam and Gepirone selectively attenuate either 20 32 or 32 64 khz ultrasonic vocalizations during aggressive encounters
Psychopharmacology, 1993Co-Authors: J. A. Vivian, Klaus A. MiczekAbstract:Ultrasonic vocalizations (USV) in rats may communicate “affective” states, as they occur only in highly significant behavioral contexts such as during sex, aggression, exposure to painful or startling events. This proposal was evaluated in an experiment with adult male Long-Evans rats during agonistic encounters; specifically, the effects of diazepam, flumazenil and Gepirone were studied on different types of USV emitted by intruder rats exposed to resident attacks and to “threat of attacks” (i.e., intruder protected within the home cage of the resident by a wire mesh cage). USV were readily emitted during agonistic encounters and consisted primarily of two distributions of pure tone whistles: 0.3- to 3-s, 20- to 32-kHz (“low”) signals and 0.02- to 0.3-s, 32- to 64-kHz (“high”) signals. A considerable repertoire of frequency modulated signals was observed and proved to be sensitive to the anxiolytic treatments. Diazepam (1–6 mg/kg) dose-dependently decreased high frequency USV during the threat of attack and decreased the mean pitch of the most predominant vocalizations but did not affect low frequency USV or the audible squeals (AS) in response to bites. Gepirone (0.3–6 mg/kg) dose-dependently decreased low frequency USV and did not affect high frequency USV or AS. Responses to thermal pain stimuli remained unaltered by all drugs, while walking duration was decreased and crouch postures were increased after diazepam but not after Gepirone administration. Gepirone in the present dose range had minimal effects on submissive, exploratory and locomotor behaviors. The pattern of results is consistent with the proposal that low frequency USV reflect a heightened affective state which is ameliorated with 5HT1A but not benzodiazepine anxiolytics, and suggests that the suppression of high frequency USV in reaction to attacks or threats coincides with the sedative or muscle relaxant properties of these compounds.
Heidi H. Swanson - One of the best experts on this subject based on the ideXlab platform.
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Antiaggresive and anxiolytic effects of Gepirone in mice, and their attenuation by WAY 100635
Pharmacology biochemistry and behavior, 1999Co-Authors: Diana L. Mendoza, Helena Aguilar Bravo, Heidi H. SwansonAbstract:The purpose of the investigation was to ascertain whether (a) the antiaggressive effects of the 5-HT1A partial agonist, Gepirone, could be mediated via its anxiolytic action; (b) the selective 5-HT1A antagonist, WAY 100635, reversed these effects, and (c) the modulation of "stress hyperthermia" could be attributed to direct effects of the drugs. Isolated male mice were treated with WAY 100635 (0, 1.5, 2.5, and 5 mg/kg) given 15 min prior to Gepirone (0, 2.5, 5, and 7.5 mg/kg). Rectal temperature was taken before the first injection and again prior to the behavioral tests. In the first session only, subjects were tested for anxiety on the elevated plus-maze before the resident-intruder test. Gepirone reduced aggression in a dose-dependent manner. This effect was counteracted by all doses of WAY 100635. On the elevated plus maze, Gepirone increased open-arm entries and duration and reduced risk assessment. The largest dose of WAY 100635 had a mild direct anxiolytic action, but all doses reduced the anxiolytic action of the largest dose of Gepirone. Body temperature was decreased dose dependently by Gepirone, an effect prevented by WAY 100635. The results justify attributing the involvement of the 5-HT1A receptors in the modulation of aggression and anxiety.
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combined effects of Gepirone and way 100135 on territorial aggression in mice
Pharmacology Biochemistry and Behavior, 1998Co-Authors: Diana Lopezmendoza, Helena Aguilarbravo, Heidi H. SwansonAbstract:Abstract LOPEZ-MENDOZA, D., H. AGUILAR-BRAVO AND H. H. SWANSON. Combined effects of Gepirone and (+)WAY 100135 on territorial aggression in mice. PHARMACOL BIOCHEM BEHAV 61 (1) 1–8, 1998.—The purpose of this investigation was to elucidate the involvement of the serotonergic 5-HT 1A system in the control of aggression. The paradigm was the response of a resident mouse to an intruder into its territory. Three experiments were performed to assess the action of various doses of Gepirone (a partial agonist) and (+)WAY 100135 (a putative antagonist), separately and in combination, on aggression and on rectal body temperature. The most consistent action of Gepirone was an increase in the latency to attack. After initiation of fighting, rates of attack, chase, and tail rattling were reduced in a dose-dependent manner by IP administration of 2.5, 5, and 10 mg/kg of Gepirone. There was no evidence of sedation or motor impairment, but autogrooming was decreased. When doses of 2.5, 5, and 10 mg/kg of (+)WAY 100135 (WAY) were given, no effects whatsoever on aggressive or other behaviors were observed. In a third experiment, a two-factor design was followed in which injection of WAY (0, 2.5, and 5 mg/kg) was followed 15 min later by injection of Gepirone (0, 2.5, 5, and 10 mg/kg). WAY decreased attack latency, increased attack rate, and attenuated the marked dose-dependent aggression reducing properties of Gepirone. The test procedure resulted in “stress hyperthermia,” which was reduced by Gepirone and increased by WAY. In both behavioral and temperature measures, the larger dose of WAY proved to be less effective than the smaller one. The results support the involvement of the 5-HT 1A system in the modulation of some forms of aggression.
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Combined Effects of Gepirone and (+)WAY 100135 on Territorial Aggression in Mice
Pharmacology biochemistry and behavior, 1998Co-Authors: Diana Lopez-mendoza, Helena Aguilar-bravo, Heidi H. SwansonAbstract:Abstract LOPEZ-MENDOZA, D., H. AGUILAR-BRAVO AND H. H. SWANSON. Combined effects of Gepirone and (+)WAY 100135 on territorial aggression in mice. PHARMACOL BIOCHEM BEHAV 61 (1) 1–8, 1998.—The purpose of this investigation was to elucidate the involvement of the serotonergic 5-HT 1A system in the control of aggression. The paradigm was the response of a resident mouse to an intruder into its territory. Three experiments were performed to assess the action of various doses of Gepirone (a partial agonist) and (+)WAY 100135 (a putative antagonist), separately and in combination, on aggression and on rectal body temperature. The most consistent action of Gepirone was an increase in the latency to attack. After initiation of fighting, rates of attack, chase, and tail rattling were reduced in a dose-dependent manner by IP administration of 2.5, 5, and 10 mg/kg of Gepirone. There was no evidence of sedation or motor impairment, but autogrooming was decreased. When doses of 2.5, 5, and 10 mg/kg of (+)WAY 100135 (WAY) were given, no effects whatsoever on aggressive or other behaviors were observed. In a third experiment, a two-factor design was followed in which injection of WAY (0, 2.5, and 5 mg/kg) was followed 15 min later by injection of Gepirone (0, 2.5, 5, and 10 mg/kg). WAY decreased attack latency, increased attack rate, and attenuated the marked dose-dependent aggression reducing properties of Gepirone. The test procedure resulted in “stress hyperthermia,” which was reduced by Gepirone and increased by WAY. In both behavioral and temperature measures, the larger dose of WAY proved to be less effective than the smaller one. The results support the involvement of the 5-HT 1A system in the modulation of some forms of aggression.