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Louis D. Van De Kar - One of the best experts on this subject based on the ideXlab platform.
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Attenuation of hormone responses to the 5-HT1A agonist Ipsapirone by long-term treatment with fluoxetine, but not desipramine, in male rats
Biological psychiatry, 1994Co-Authors: S Brownfield Mark, Andrew D. Levy, George Battaglia, Theresa M. Cabrera, Louis D. Van De KarAbstract:The present study had two objectives: (1) to provide information on neuroendocrine challenge tests that can lead to diagnostic tests in humans; and (2) to confirm our previous observation that chronic fluoxetine selectively inhibits serotonin (5-HT1A) receptor function. We determined the effect of chronic fluoxetine and desipramine (DMI) on the hormone response to Ipsapirone, a 5-HT1A agonist and a potential anxiolytic drug. Ipsapirone increased oxytocin, adrenocorticotropic hormone (ACTH), corticosterone, and prolactin, but not renin or vasopressin concentrations in plasma. Chronic fluoxetine, but not DMI, significantly inhibited the effect of Ipsapirone on plasma oxytocin, ACTH and corticosterone concentrations. Chronic fluoxetine also reduced the Bmax for 3H-8-hydroxy-2-(dipropylamino) tetralin (3H-8-OH-DPAT) labelled 5-HT1A receptors in the midbrain. Neither antidepressant altered the density or affinity of 5-HT uptake sites. In conclusion, the present results confirm our previous results using 8-OH-DPAT as a challenge, and suggest that chronic 5-HT uptake inhibition results in adaptive changes leading to decreased function of the 5-HT1A receptor system. Finally, because Ipsapirone may be administered to humans, it might be usable to evaluate 5-HT1A receptor function in depressed patients.
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Comparison of neuroendocrine and behavioral effects of Ipsapirone, a 5-HT1A agonist, in three stress paradigms: immobilization, forced swim and conditioned fear.
Brain Research, 1992Co-Authors: Peter A. Rittenhouse, Erica A. Bakkum, Patricia A. O'connor, Molly Carnes, Cynthia L. Bethea, Louis D. Van De KarAbstract:Ipsapirone is an anxiolytic drug and a serotonin1A (5-HT1A) agonist. The aim of the present study was to investigate the effects of low doses of Ipsapirone on the hormonal and behavioral response to three stress procedures: immobilization, forced swim and conditioned emotional response (CER). We examined the effect of Ipsapirone (0.1, 0.5 or 1.0 mg/kg) on plasma renin concentration (PRC), adrenal corticotropic hormone (ACTH), corticosterone, prolactin and defacation in rats exposed to immobilization, forced swim or CER stress. All three stressors significantly elevated all the hormone levels (P < 0.01). Immobilization-induced elevations of PRC, and corticosterone were inhibited by the highest doses of Ipsapirone (0.5 and 1 mg/kg, i.p.). However, Ipsapirone did not modify the immobilization-induced elevations of plasma ACTH, prolactin or defecation. Ipsapirone was relatively ineffective at reducing the endocrine responses to forced swim. Ipsapirone reduced some, but not all of the hormonal responses to CER stress. CER-induced elevations of corticosterone and prolactin were not inhibited by Ipsapirone. However, the ACTH response to CER was significantly (P < 0.01) inhibited by all doses of Ipsapirone and the highest dose of Ipsapirone attenuated the renin response. In contrast with the hormonal responses, Ipsapirone inhibited all of the behavioral responses to CER stress. Ipsapirone inhibited CER-induced freezing behavior and defecation, while dose-dependently reversing the suppressive effect of CER on exploring, grooming and rearing behaviors. In conclusion, there is a dissociation between the influence of Ipsapirone on the endocrine and behavioral responses to CER stress. Ipsapirone also has differential effects on the neuroendocrine response to the three stressors studied. Ipsapirone was most effective in attenuating the hormonal responses to CER, followed by immobilization and swim stress. Of the hormones studied, the stimulation of renin secretion after exposure to the three stressors was most sensitive to Ipsapirone, while corticosterone and prolactin were the least sensitive to Ipsapirone.
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Comparison of neuroendocrine and behavioral effects of Ipsapirone, a 5-HT1A agonist, in three stress paradigms: immobilization, forced swim and conditioned fear.
Brain research, 1992Co-Authors: Peter A. Rittenhouse, Erica A. Bakkum, Patricia A. O'connor, Molly Carnes, Cynthia L. Bethea, Louis D. Van De KarAbstract:Ipsapirone is an anxiolytic drug and a serotonin1A (5-HT1A) agonist. The aim of the present study was to investigate the effects of low doses of Ipsapirone on the hormonal and behavioral response to three stress procedures: immobilization, forced swim and conditioned emotional response (CER). We examined the effect of Ipsapirone (0.1, 0.5 or 1.0 mg/kg) on plasma renin concentration (PRC), adrenal corticotropic hormone (ACTH), corticosterone, prolactin and defecation in rats exposed to immobilization, forced swim or CER stress. All three stressors significantly elevated all the hormone levels (P less than 0.01). Immobilization-induced elevations of PRC, and corticosterone were inhibited by the highest doses of Ipsapirone (0.5 and 1 mg/kg, i.p.). However, Ipsapirone did not modify the immobilization-induced elevations of plasma ACTH, prolactin or defecation. Ipsapirone was relatively ineffective at reducing the endocrine responses to forced swim. Ipsapirone reduced some, but not all of the hormonal responses to CER stress. CER-induced elevations of corticosterone and prolactin were not inhibited by Ipsapirone. However, the ACTH response to CER was significantly (P less than 0.01) inhibited by all doses of Ipsapirone and the highest dose of Ipsapirone attenuated the renin response. In contrast with the hormonal responses, Ipsapirone inhibited all of the behavioral responses to CER stress. Ipsapirone inhibited CER-induced freezing behavior and defecation, while dose-dependently reversing the suppressive effect of CER on exploring, grooming and rearing behaviors. In conclusion, there is a dissociation between the influence of Ipsapirone on the endocrine and behavioral responses to CER stress. Ipsapirone also has differential effects on the neuroendocrine response to the three stressors studied. Ipsapirone was most effective in attenuating the hormonal responses to CER, followed by immobilization and swim stress. Of the hormones studied, the stimulation of renin secretion after exposure to the three stressors was most sensitive to Ipsapirone, while corticosterone and prolactin were the least sensitive to Ipsapirone.
Jean De Vry - One of the best experts on this subject based on the ideXlab platform.
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Effects of the 5-HT1A receptor agonist Ipsapirone on operant self-administration of ethanol in the rat.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 1999Co-Authors: Rudy Schreiber, Birgit Manze, Annette Haussels, Jean De VryAbstract:Although the serotonin (5-HT)1A receptor agonist Ipsapirone reduces ethanol intake in a variety of animal models of alcoholism, such effects have only been reported in models based on nonoperant behavior (e.g., two-bottle choice procedures). It was the aim of the present study to characterize the effects of Ipsapirone in an operant model of alcohol self-administration. Rats were trained during daily 30-min sessions to respond for oral delivery of an ethanol solution (10% w/v) or water in a two-lever, fixed-ratio:1, saccharin-fading procedure. After establishment of stable responding, Ipsapirone (0, 2.5–20 mg/kg, intraperitoneal) was tested in combination with different ethanol unit doses (0, 1.25–20%). Ethanol-reinforced responding was related to the ethanol unit dose in an inverted U-shaped manner. Ipsapirone dose-dependently decreased the number of ethanol- and water-reinforced lever responses, irrespective of the ethanol unit dose, and failed to affect ethanol preference. As there was only a minor difference between the minimal effective dose which reduced operant responding for ethanol and water (i.e., 10 and 20 mg/kg, respectively), and there was no evidence for a drug-induced left- or rightward shift of the ethanol unit dose–response curve, the effects of Ipsapirone are considered to be nonselective. It is suggested that the ethanol intake-reducing effects of Ipsapirone are not the result of a drug-induced interference (either of an attenuating, or potentiating, nature) with the positive reinforcing stimulus properties of alcohol.
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Effect of repeated Ipsapirone treatment on hippocampal excitatory synaptic transmission in the freely behaving rat: role of 5-HT1A receptors and relationship to anxiolytic effect
European journal of pharmacology, 1997Co-Authors: Roger Anwyl, Jean De Vry, Michael J. RowanAbstract:Abstract The effects of acute and repeated treatment with the 5-HT 1A receptor ligand Ipsapirone on hippocampal excitatory synaptic transmission and in an ultrasonic vocalization anxiety test were investigated in the rat. Synaptic responses in the CA1 region of the dorsal hippocampus of alert, freely behaving male Wistar rats were reduced after acute injection of Ipsapirone (1 or 2 mg/kg, i.p.). This effect was prevented by pretreatment with the 5-HT 1A receptor antagonist WAY-100635 ( N -[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N -(2-pyridinyl)cyclohexanecarboxamide trihydrochloride, 0.25 or 0.5 mg/kg, i.p.) but not by the 5-HT-depleting agent para -chlorophenylalanine (300 mg/kg per day for 3 days, i.p.). WAY-100635 (0.1–0.3 mg/kg, i.p.) also blocked the acute anti-aversive effects of Ipsapirone (3 mg/kg, i.p.) in the anxiety test. Repeated administration of Ipsapirone (1 or 2 mg/kg per day for 7–8 days, i.p.) produced a gradual reduction in baseline synaptic transmission which was transiently reversed by WAY-100635 (0.25 mg/kg, i.p.). Ipsapirone (1 mg/kg per day for 7 days) produced a gradual and sustained reduction in the duration of vocalizations in the anxiety test which paralleled the reduction in baseline synaptic responses in the same animals. The data indicate that with repeated administration of Ipsapirone, a prolongation and enhancement of the 5-HT 1A receptor-mediated reduction in hippocampal excitatory synaptic transmission occurs. This delayed effect may contribute to the sustained anxiolytic and/or antidepressant effect of Ipsapirone. © 1997 Elsevier Science B.V. All rights reserved.
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Effect of repeated Ipsapirone treatment on hippocampal excitatory synaptic transmission in the freely behaving rat: role of 5-HT receptors
1997Co-Authors: Roger Anwyl, Jean De Vry, Michael J. RowanAbstract:AbstractThe effects of acute and repeated treatment with the 5-HT receptor ligand Ipsapirone on hippocampal excitatory synaptic 1A transmission and in an ultrasonic vocalization anxiety test were investigated in the rat. Synaptic responses in the CA1 region of the dorsalhippocampus of alert, freely behaving male Wistar rats were reduced after acute injection of Ipsapirone 1 or 2 mg.rkg, i.p. . This effectwas prevented by pretreatment with the 5-HT receptor antagonist WAY-100635 N- 2- 4- 2-methoxyphenyl -1-piperazinyl ethyl -ww.xx- 1A .2-pyridinyl cyclo-hexanecarboxamide trihydrochloride, 0.25 or 0.5 mgrkg, i.p. but not by the 5-HT-depleting agent.para-chlorophenylalanine 300mg rkg per day for 3 days, i.p. . WAY-100635 0.1–0.3 mg. . kg, i.p. also blocked the acute anti-aversive effects of Ipsapirone 3 mg kg,i.p. in the anxiety test. Repeated administration of Ipsapirone 1 or 2 mg..rkg per day for 7–8 days, i.p. produced a gradual reduction inbaseline synaptic transmission which was transiently reversed by WAY-100635 0.25 mg.rkg, i.p. . Ipsapirone 1 mg kg per day for 7days produced a gradual and sustained reduction in the duration of vocalizations in the anxiety test which paralleled the reduction in.baseline synaptic responses in the same animals. The data indicate that with repeated administration of Ipsapirone, a prolongation andenhancement of the 5-HT receptor-mediated reduction in hippocampal excitatory synaptic transmission occurs. This delayed effect may
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Neuronal circuits involved in the anxiolytic effects of the 5-HT1A receptor agonists 8-OH-DPAT Ipsapirone and buspirone in the rat.
European journal of pharmacology, 1993Co-Authors: Rudy Schreiber, Jean De VryAbstract:In rats, the 5-HT1A receptor full agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the 5-HT1A receptor partial agonists Ipsapirone and buspirone dose dependently and completely inhibited shock-induced ultrasonic vocalization after systemic injection and after microinjection into the dorsal raphe nucleus, a brain region rich in somatodendritic 5-HT1A receptors. As compared with injection into the dorsal raphe nucleus, Ipsapirone and 8-OH-DPAT were significantly less potent after microinjection into the lateral ventricle or the median raphe nucleus. Depletion of brain 5-HT (5-hydroxytryptamine) by means of 5,7-dihydroxytryptamine or parachlorophenylalanine inhibited ultrasonic vocalization. In lesioned rats, however, Ipsapirone (i.p. or dorsal raphe nucleus) and 8-OH-DPAT (dorsal raphe nucleus) retained their ability to inhibit ultrasonic vocalization and, in non-lesioned rats, bilateral injection of Ipsapirone, buspirone and 8-OH-DPAT into the dorsal hippocampus and the amygdala - two brain regions rich in postsynaptic 5-HT1A receptors - also inhibited ultrasonic vocalization. In a Geller-Seifter conflict test, i.p. and local injection of 8-OH-DPAT in the dorsal raphe nucleus and the hippocampus selectively enhanced punished responding. It is suggested that both presynaptic and (possibly to a lesser extent) postsynaptic 5-HT1A receptors are involved in the anxiolytic effects of Ipsapirone, buspirone, and 8-OH-DPAT.
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comparison of acute and repeated treatment with the 5 ht1a receptor ligands 8 oh dpat and Ipsapirone in animal models of anxiety and depression
Drug Development Research, 1993Co-Authors: Jean De Vry, Rudy SchreiberAbstract:The present study compared the 5-HT1A receptor ligands 8-OH-DPAT and Ipsapirone with diazpepam and imipramine in the shock induced ultrasonic vocalization anxiety test and the forced swimming depression test in the rat. Acutely, 8-OH-DPAT induced anxiolytic and antidepressive effects (ED50: 0.12 and 1.4 mg/kg, i.p., respectively), whereas Ipsapirone induced anxiolytic (ED50: 0.6 mg/kg) and moderate antidepressive effects (33% at 3-10 mg/kg). Virtually no tolerance developed for the anxiolytic effects after 2 weeks of treatment with 0.03-1 mg/kg 8-OH-DPAT or 0.1-10 mg/kg Ipsapirone (i.p., b.i.d.), with 10 mg/kg/day Ipsapirone (s.c., mini-pumps), or with 1.5 μg/rat/hr 8-OH-DPAT (local infusion in the dorsal raphe nucleus, mini-pumps). However, some tolerance developed for the antidepressive effects of 8-OH-DPAT (ED50: 0.6, 1.4, 2.5 and >3 mg/kg, after 2 weeks of pretreatment with vehicle, 0.3, 1, and 3 mg/kg 8-OH-DPAT, respectively, i.p., b.i.d.). In the case of Ipsapirone, the dose-effect curve in the forced swimming test was shifted to the left after 2 weeks of pretreatment with Ipsapirone (0.3-10 mg/kg, i.p., b.i.d.). Acutely, diazepam induced an anxiolytic effect (ED50: 3.6 mg/kg, i.p.), but failed to induce an antidepressive effect; whereas imipramine induced an antidepressive effect (ED50: 20.5 mg/kg) and a moderate anxiolytic effect (max. efficacy: 47% at 30 mg/kg). Upon repeated administration (2 weeks), diazepam (5 mg/kg) showed t0olerance for its anxiolytic effects and weak antidepressive effects emerged, whereas imipramine (20 mg/kg) showed weak sensitization for both effects. It is concluded that (a) with all compounds, tolerance, as well as sensitization can be observed, depending on the behavioral test, the dose and the type of compound; and (b) compared with the other compounds tested, relatively low doses of 5-HT1A drugs offer the most attractive profile of mixed anxiolytic/antidepressive activity. © 1993 wiley-Liss, Inc.
Peter A. Rittenhouse - One of the best experts on this subject based on the ideXlab platform.
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Comparison of neuroendocrine and behavioral effects of Ipsapirone, a 5-HT1A agonist, in three stress paradigms: immobilization, forced swim and conditioned fear.
Brain Research, 1992Co-Authors: Peter A. Rittenhouse, Erica A. Bakkum, Patricia A. O'connor, Molly Carnes, Cynthia L. Bethea, Louis D. Van De KarAbstract:Ipsapirone is an anxiolytic drug and a serotonin1A (5-HT1A) agonist. The aim of the present study was to investigate the effects of low doses of Ipsapirone on the hormonal and behavioral response to three stress procedures: immobilization, forced swim and conditioned emotional response (CER). We examined the effect of Ipsapirone (0.1, 0.5 or 1.0 mg/kg) on plasma renin concentration (PRC), adrenal corticotropic hormone (ACTH), corticosterone, prolactin and defacation in rats exposed to immobilization, forced swim or CER stress. All three stressors significantly elevated all the hormone levels (P < 0.01). Immobilization-induced elevations of PRC, and corticosterone were inhibited by the highest doses of Ipsapirone (0.5 and 1 mg/kg, i.p.). However, Ipsapirone did not modify the immobilization-induced elevations of plasma ACTH, prolactin or defecation. Ipsapirone was relatively ineffective at reducing the endocrine responses to forced swim. Ipsapirone reduced some, but not all of the hormonal responses to CER stress. CER-induced elevations of corticosterone and prolactin were not inhibited by Ipsapirone. However, the ACTH response to CER was significantly (P < 0.01) inhibited by all doses of Ipsapirone and the highest dose of Ipsapirone attenuated the renin response. In contrast with the hormonal responses, Ipsapirone inhibited all of the behavioral responses to CER stress. Ipsapirone inhibited CER-induced freezing behavior and defecation, while dose-dependently reversing the suppressive effect of CER on exploring, grooming and rearing behaviors. In conclusion, there is a dissociation between the influence of Ipsapirone on the endocrine and behavioral responses to CER stress. Ipsapirone also has differential effects on the neuroendocrine response to the three stressors studied. Ipsapirone was most effective in attenuating the hormonal responses to CER, followed by immobilization and swim stress. Of the hormones studied, the stimulation of renin secretion after exposure to the three stressors was most sensitive to Ipsapirone, while corticosterone and prolactin were the least sensitive to Ipsapirone.
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Comparison of neuroendocrine and behavioral effects of Ipsapirone, a 5-HT1A agonist, in three stress paradigms: immobilization, forced swim and conditioned fear.
Brain research, 1992Co-Authors: Peter A. Rittenhouse, Erica A. Bakkum, Patricia A. O'connor, Molly Carnes, Cynthia L. Bethea, Louis D. Van De KarAbstract:Ipsapirone is an anxiolytic drug and a serotonin1A (5-HT1A) agonist. The aim of the present study was to investigate the effects of low doses of Ipsapirone on the hormonal and behavioral response to three stress procedures: immobilization, forced swim and conditioned emotional response (CER). We examined the effect of Ipsapirone (0.1, 0.5 or 1.0 mg/kg) on plasma renin concentration (PRC), adrenal corticotropic hormone (ACTH), corticosterone, prolactin and defecation in rats exposed to immobilization, forced swim or CER stress. All three stressors significantly elevated all the hormone levels (P less than 0.01). Immobilization-induced elevations of PRC, and corticosterone were inhibited by the highest doses of Ipsapirone (0.5 and 1 mg/kg, i.p.). However, Ipsapirone did not modify the immobilization-induced elevations of plasma ACTH, prolactin or defecation. Ipsapirone was relatively ineffective at reducing the endocrine responses to forced swim. Ipsapirone reduced some, but not all of the hormonal responses to CER stress. CER-induced elevations of corticosterone and prolactin were not inhibited by Ipsapirone. However, the ACTH response to CER was significantly (P less than 0.01) inhibited by all doses of Ipsapirone and the highest dose of Ipsapirone attenuated the renin response. In contrast with the hormonal responses, Ipsapirone inhibited all of the behavioral responses to CER stress. Ipsapirone inhibited CER-induced freezing behavior and defecation, while dose-dependently reversing the suppressive effect of CER on exploring, grooming and rearing behaviors. In conclusion, there is a dissociation between the influence of Ipsapirone on the endocrine and behavioral responses to CER stress. Ipsapirone also has differential effects on the neuroendocrine response to the three stressors studied. Ipsapirone was most effective in attenuating the hormonal responses to CER, followed by immobilization and swim stress. Of the hormones studied, the stimulation of renin secretion after exposure to the three stressors was most sensitive to Ipsapirone, while corticosterone and prolactin were the least sensitive to Ipsapirone.
Stephen M Stahl - One of the best experts on this subject based on the ideXlab platform.
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effectiveness of Ipsapirone a 5 ht 1a partial agonist in major depressive disorder support for the role of 5 ht 1a receptors in the mechanism of action of serotonergic antidepressants
The International Journal of Neuropsychopharmacology, 1998Co-Authors: Stephen M Stahl, Lee Kaiser, Julie Roeschen, Jan Keppel M Hesselink, John OrazemAbstract:Desensitisation of serotonin 1A (5-HT-1A) receptors is a leading hypothesis for the mechanism of action of antidepressants which block serotonin reuptake. This hypothesis predicts that direct-acting 5-HT-1A agonists should also exhibit anti-depressant properties. Here we report the results of the first large-scale controlled study of the efficacy and tolerability of a 5-HT-1A agonist in outpatients with major depressive disorder (MDD). Three hundred and seventy-three subjects meeting DSM-III-R criteria for MDD participated in this randomised, double-blind comparison of the 5-HT-1A partial agonist Ipsapirone (5 mg, 7.5 mg and 10 mg t.i.d.) to placebo t.i.d. Improvement in depressive symptoms relative to placebo, as measured by the Hamilton Depression Rating Scale, occurred in the Ipsapirone (7.5 mg t.i.d.) group with a magnitude of effect (D=-2.53 points) that was statistically significant (p=0.010). Adverse events occurred in 76% of the placebo patients and 92% of the Ipsapirone patients. A dose-related increase in the incidence of adverse events led to discontinuation of treatment with the 10 mg t.i.d. Results of this study demonstrate that Ipsapirone, at a dose of 7.5 mg t.i.d., is an effective antidepressant agent in the treatment of MDD, supporting the hypothesised role of 5-HT-1A receptors in the mechanism of action of serotonin reuptake inhibitors. However, as a potential therapeutic agent for depression, Ipsapirone shows only a modest magnitude of drug-placebo differences as well as a side-effect profile less favorable than many of the newer antidepressants.
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Ipsapirone, a 5-HT_1A Agonist, Suppresses REM Sleep Equally in Unmedicated Depressed Patients and Normal Controls
Neuropsychopharmacology, 1996Co-Authors: J Christian Gillin, Mark Rapaport, John Kelsoe, Jin-wook Sohn, Stephen M Stahl, Michael Lardon, Caroline Ruiz, Shah GolshanAbstract:To determine whether Ipsapirone, a 5-HT_1A agonist, differentially suppresses REM sleep in depressed patients compared with normal controls, we administered placebo, Ipsapirone 10 mg, or Ipsapirone 20 mg in a double-blind, random order before bedtime in 18 unmedicated patients with depression and 16 age-matched, gender-matched normal controls. Compared to placebo, Ipsapirone affected REM sleep measures equally in depressed patients and controls as follows: (1) increased REM latency; (2) reduced total REM percent, REM time, and REM density; and (3) delayed the onset of REM sleep. In addition, Ipsapirone had similar effects in patients and controls in other sleep measures: (1) reduced total sleep time; (2) delayed sleep onset time; and (3) increased sleep latency, stage 1%, stage 2%, the amount of stage 3 & 4 sleep in the first non-REM period, and wake time after sleep onset. The study does not support the hypothesis that downregulated 5-HT_1A receptors mediate the pathophysiology or sleep disturbances of depression, although further studies are needed as these patients did not differ from controls in baseline sleep measures.
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Ipsapirone, a 5-HT1A agonist, suppresses REM sleep equally in unmedicated depressed patients and normal controls.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 1996Co-Authors: J Christian Gillin, Jin-wook Sohn, Stephen M Stahl, Michael Lardon, Caroline Ruiz, John R. Kelsoe, Mark Hyman Rapaport, Shah GolshanAbstract:To determine whether Ipsapirone, a 5-HT1A agonist, differentially suppresses REM sleep in depressed patients compared with normal controls, we administered placebo, Ipsapirone 10 mg, or Ipsapirone 20 mg in a double-blind, random order before bedtime in 18 unmedicated patients with depression and 16 age-matched, gender-matched normal controls. Compared to placebo, Ipsapirone affected REM sleep measures equally in depressed patients and controls as follows: (1) increased REM latency; (2) reduced total REM percent, REM time, and REM density; and (3) delayed the onset of REM sleep. In addition, Ipsapirone had similar effects in patients and controls in other sleep measures: (1) reduced total sleep time; (2) delayed sleep onset time; and (3) increased sleep latency, stage 1%, stage 2%, the amount of stage 3 & 4 sleep in the first non-REM period, and wake time after sleep onset. The study does not support the hypothesis that downregulated 5-HT1A receptors mediate the pathophysiology or sleep disturbances of depression, although further studies are needed as these patients did not differ from controls in baseline sleep measures.
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Inhibition of REM sleep by Ipsapirone, A 5HT1_A agonist, in normal volunteers
Psychopharmacology, 1994Co-Authors: J Christian Gillin, Michael Lardon, Shah Golshan, Wojciech Jernajczyk, Dirceu De C. Valladares-neto, Stephen M StahlAbstract:In order to test the hypothesis that serotonergic mechanisms inhibit REM sleep via a 5HT1_A receptor, we administered placebo and Ipsapirone (10 and 20 mg by mouth 15 min before bedtime) to ten normal volunteers in a double blind fashion. Ipsapirone is a relatively selective 5HT1_A receptor agonist. As predicted, Ipsapirone prolonged REM latency and Mean Latency to Eye Movements (M-LEM), a measure of time between onset of REM sleep and the first eye movement of the REM period, and REM% at both doses compared with placebo. It also reduced sleep efficiency and total REM sleep time at the highest dose. These results support the hypothesis that systemic stimulation of 5HT1_A receptors prolong REM latency and inhibit REM sleep.
Cynthia L. Bethea - One of the best experts on this subject based on the ideXlab platform.
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Comparison of neuroendocrine and behavioral effects of Ipsapirone, a 5-HT1A agonist, in three stress paradigms: immobilization, forced swim and conditioned fear.
Brain Research, 1992Co-Authors: Peter A. Rittenhouse, Erica A. Bakkum, Patricia A. O'connor, Molly Carnes, Cynthia L. Bethea, Louis D. Van De KarAbstract:Ipsapirone is an anxiolytic drug and a serotonin1A (5-HT1A) agonist. The aim of the present study was to investigate the effects of low doses of Ipsapirone on the hormonal and behavioral response to three stress procedures: immobilization, forced swim and conditioned emotional response (CER). We examined the effect of Ipsapirone (0.1, 0.5 or 1.0 mg/kg) on plasma renin concentration (PRC), adrenal corticotropic hormone (ACTH), corticosterone, prolactin and defacation in rats exposed to immobilization, forced swim or CER stress. All three stressors significantly elevated all the hormone levels (P < 0.01). Immobilization-induced elevations of PRC, and corticosterone were inhibited by the highest doses of Ipsapirone (0.5 and 1 mg/kg, i.p.). However, Ipsapirone did not modify the immobilization-induced elevations of plasma ACTH, prolactin or defecation. Ipsapirone was relatively ineffective at reducing the endocrine responses to forced swim. Ipsapirone reduced some, but not all of the hormonal responses to CER stress. CER-induced elevations of corticosterone and prolactin were not inhibited by Ipsapirone. However, the ACTH response to CER was significantly (P < 0.01) inhibited by all doses of Ipsapirone and the highest dose of Ipsapirone attenuated the renin response. In contrast with the hormonal responses, Ipsapirone inhibited all of the behavioral responses to CER stress. Ipsapirone inhibited CER-induced freezing behavior and defecation, while dose-dependently reversing the suppressive effect of CER on exploring, grooming and rearing behaviors. In conclusion, there is a dissociation between the influence of Ipsapirone on the endocrine and behavioral responses to CER stress. Ipsapirone also has differential effects on the neuroendocrine response to the three stressors studied. Ipsapirone was most effective in attenuating the hormonal responses to CER, followed by immobilization and swim stress. Of the hormones studied, the stimulation of renin secretion after exposure to the three stressors was most sensitive to Ipsapirone, while corticosterone and prolactin were the least sensitive to Ipsapirone.
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Comparison of neuroendocrine and behavioral effects of Ipsapirone, a 5-HT1A agonist, in three stress paradigms: immobilization, forced swim and conditioned fear.
Brain research, 1992Co-Authors: Peter A. Rittenhouse, Erica A. Bakkum, Patricia A. O'connor, Molly Carnes, Cynthia L. Bethea, Louis D. Van De KarAbstract:Ipsapirone is an anxiolytic drug and a serotonin1A (5-HT1A) agonist. The aim of the present study was to investigate the effects of low doses of Ipsapirone on the hormonal and behavioral response to three stress procedures: immobilization, forced swim and conditioned emotional response (CER). We examined the effect of Ipsapirone (0.1, 0.5 or 1.0 mg/kg) on plasma renin concentration (PRC), adrenal corticotropic hormone (ACTH), corticosterone, prolactin and defecation in rats exposed to immobilization, forced swim or CER stress. All three stressors significantly elevated all the hormone levels (P less than 0.01). Immobilization-induced elevations of PRC, and corticosterone were inhibited by the highest doses of Ipsapirone (0.5 and 1 mg/kg, i.p.). However, Ipsapirone did not modify the immobilization-induced elevations of plasma ACTH, prolactin or defecation. Ipsapirone was relatively ineffective at reducing the endocrine responses to forced swim. Ipsapirone reduced some, but not all of the hormonal responses to CER stress. CER-induced elevations of corticosterone and prolactin were not inhibited by Ipsapirone. However, the ACTH response to CER was significantly (P less than 0.01) inhibited by all doses of Ipsapirone and the highest dose of Ipsapirone attenuated the renin response. In contrast with the hormonal responses, Ipsapirone inhibited all of the behavioral responses to CER stress. Ipsapirone inhibited CER-induced freezing behavior and defecation, while dose-dependently reversing the suppressive effect of CER on exploring, grooming and rearing behaviors. In conclusion, there is a dissociation between the influence of Ipsapirone on the endocrine and behavioral responses to CER stress. Ipsapirone also has differential effects on the neuroendocrine response to the three stressors studied. Ipsapirone was most effective in attenuating the hormonal responses to CER, followed by immobilization and swim stress. Of the hormones studied, the stimulation of renin secretion after exposure to the three stressors was most sensitive to Ipsapirone, while corticosterone and prolactin were the least sensitive to Ipsapirone.
