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Gabriel Nowak - One of the best experts on this subject based on the ideXlab platform.
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Effects of acute and chronic treatment with magnesium in the Forced Swim Test in rats.
Pharmacological Reports, 2020Co-Authors: Ewa Poleszak, Andrzej Pilc, Piotr Wlaź, Ewa Kędzierska, Maria Radziwoń-zaleska, Sylwia Fidecka, Gabriel NowakAbstract:The antidepressant-like activity of magnesium, the non-specific N-methyl-D-aspartate glutamate receptor antagonist, in the mice Forced Swim Test was demonstrated previously. In the present study, the effects of this biometal were studied in the rat Forced Swim Test. Magnesium (MgCl 2 ) at doses ranging from 15 to 50 mg Mg/kg reduced the immobility time in the Forced Swim Test, thus exerting antidepressant-like activity. To evaluate tolerance to this effect, we also performed experiments with the following acute/chronic magnesium treatment schedule: chronic saline and saline challenge at 0.5 h before behavioral experiments (S + S), chronic saline and magnesium challenge (S + Mg), chronic magnesium and saline challenge (Mg + S), chronic magnesium and magnesium challenge (Mg + Mg). The antidepressant-like effect of magnesium was demonstrated in the group treated acutely with magnesium (S + Mg) but not in the chronically treated group (Mg + S) and (Mg + Mg). It is interesting to note that in Mg + Mg group serum concentration of magnesium was quite similar to the S + Mg group (6.44 vs. 6.08 mg/100 ml, respectively), which displayed antidepressant-like effect. The results confirmed that magnesium administered acutely induced the antidepressant-like effects also in rats. However, contrary to mice, chronic treatment with magnesium induced tolerance to this effect in rats.
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Antidepressant-like effects of ketamine, norketamine and dehydronorketamine in Forced Swim Test: Role of activity at NMDA receptor
Neuropharmacology, 2015Co-Authors: Kinga Sałat, Gabriel Nowak, Gabriela Starowicz, Tadeusz Librowski, Urszula Drabik, Ryszard Gajdosz, Agata Siwek, Piotr PopikAbstract:Ketamine produces rapid and long-lasting antidepressant effects in patients. The involvement of ketamine metabolites in these actions has been proposed. The effects of ketamine and its metabolites norketamine and dehydronorketamine on ligand binding to 80 receptors, ion channels and transporters was investigated at a single concentration of 10 μM. The affinities of all three compounds were then assessed at NMDA receptors using [3H]MK-801 binding. The dose-response relationships of all 3 compounds in the Forced Swim Test were also investigated in mice 30 min after IP administration. The effects of ketamine and norketamine (both 50 mg/kg) were then examined at 30 min, 3 days and 7 days post administration. Among the 80 potential targets examined, only NMDA receptors were affected with a magnitude of >50% by ketamine and norketamine at the concentration of 10 μM. The Ki values of ketamine, norketamine and dehydronorketamine at NMDA receptors were 0.119 ± 0.01, 0.97 ± 0.1 and 3.21 ± 0.3 μM, respectively. Ketamine and norketamine reduced immobility with minimum effective doses (MEDs) of 10 and 50 mg/kg, respectively; dehydronorketamine did not affect immobility at doses of up to 50 mg/kg. Neither ketamine nor norketamine reduced immobility in the Forced Swim Test 3 and 7 days following administration. Further, oral administration of ketamine (5-50 mg/kg) did not affect immobility. We demonstrate that ketamine and norketamine but not dehydronorketamine given acutely at subanesthetic doses reduced immobility in the Forced Swim Test. These antidepressant-like effects appear attributable to NMDA receptor inhibition.
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a complex interaction between glycine nmda receptors and serotonergic noradrenergic antidepressants in the Forced Swim Test in mice
Journal of Neural Transmission, 2011Co-Authors: Ewa Poleszak, Andrzej Wróbel, Gabriel Nowak, Regina Kasperek, Bernadeta Szewczyk, Piotr Wlaź, Aleksandra WlaźAbstract:Both clinical and preclinical studies demonstrate the antidepressant activity of the functional NMDA receptor antagonists. In this study, we assessed the effects of two glycine/NMDA receptor ligands, namely L-701,324 (antagonist) and d-cycloserine (a partial agonist) on the action of antidepressant drugs with different pharmacological profiles in the Forced Swim Test in mice. Swim sessions were conducted by placing mice individually in glass cylinders filled with warmed water for 6 min. The duration of behavioral immobility during the last 4 min of the Test was evaluated. The locomotor activity of mice was measured with photoresistor actimeters. L-701,324 and d-cycloserine given with reboxetine (administered in subeffective doses) did not change the behavior of animals in the Forced Swim Test. A potentiating effect was seen when both Tested glycine site ligands were given concomitantly with imipramine or fluoxetine in this Test. The lesion of noradrenaline nerve terminals produced by DSP-4 neither altered the baseline activity nor influenced the antidepressant-like action of L-701,324 or d-cycloserine. The depletion of serotonin by p-CPA did not alter baseline activity in the Forced Swim Test. However, it completely antagonized the antidepressant-like action produced by L-701,324 and d-cycloserine. Moreover, the antidepressant-like effects of imipramine, fluoxetine and reboxetine were abolished by d-serine, a full agonist of glycine/NMDA receptors. The present study demonstrates that glycine/NMDA receptor functional antagonists enhance the antidepressant-like action of serotonin, but not noradrenaline-based antidepressants and such their activity seems to depend on serotonin rather than noradrenaline pathway.
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A complex interaction between glycine/NMDA receptors and serotonergic/noradrenergic antidepressants in the Forced Swim Test in mice
Journal of Neural Transmission, 2011Co-Authors: Ewa Poleszak, Andrzej Wróbel, Aleksandra Wlaź, Regina Kasperek, Piotr Wlaź, Bernadeta Szewczyk, Gabriel NowakAbstract:Both clinical and preclinical studies demonstrate the antidepressant activity of the functional NMDA receptor antagonists. In this study, we assessed the effects of two glycine/NMDA receptor ligands, namely L-701,324 (antagonist) and D: -cycloserine (a partial agonist) on the action of antidepressant drugs with different pharmacological profiles in the Forced Swim Test in mice. Swim sessions were conducted by placing mice individually in glass cylinders filled with warmed water for 6 min. The duration of behavioral immobility during the last 4 min of the Test was evaluated. The locomotor activity of mice was measured with photoresistor actimeters. L-701,324 and D: -cycloserine given with reboxetine (administered in subeffective doses) did not change the behavior of animals in the Forced Swim Test. A potentiating effect was seen when both Tested glycine site ligands were given concomitantly with imipramine or fluoxetine in this Test. The lesion of noradrenaline nerve terminals produced by DSP-4 neither altered the baseline activity nor influenced the antidepressant-like action of L-701,324 or D: -cycloserine. The depletion of serotonin by p-CPA did not alter baseline activity in the Forced Swim Test. However, it completely antagonized the antidepressant-like action produced by L-701,324 and D: -cycloserine. Moreover, the antidepressant-like effects of imipramine, fluoxetine and reboxetine were abolished by D: -serine, a full agonist of glycine/NMDA receptors. The present study demonstrates that glycine/NMDA receptor functional antagonists enhance the antidepressant-like action of serotonin, but not noradrenaline-based antidepressants and such their activity seems to depend on serotonin rather than noradrenaline pathway.
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Lack of NMDA–AMPA interaction in antidepressant-like effect of CGP 37849, an antagonist of NMDA receptor, in the Forced Swim Test
Journal of Neural Transmission, 2008Co-Authors: Małgorzata Dybała, Agata Siwek, Ewa Poleszak, Andrzej Pilc, Gabriel NowakAbstract:The NMDA receptor antagonist, CGP 37849-induced reduction in immobility time in the Forced Swim Test in mice was not antagonized by pre-treatment with the AMPA receptor antagonist NBQX. This is the first demonstration of the antidepressant effect of the NMDA antagonist not being dependent on the AMPA transmission.
Shirish P. Jain - One of the best experts on this subject based on the ideXlab platform.
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antidepressant like effect of the neurosteroid 3α hydroxy 5α pregnan 20 one in mice Forced Swim Test
Pharmacology Biochemistry and Behavior, 2000Co-Authors: R. T. Khisti, Chandrabhan T. Chopde, Shirish P. JainAbstract:The present study aimed to examine the antidepressant-like effect of the neurosteroid 3α-hydroxy-5α-pregnan-20-one (3α, 5α THP) using the Forced Swim Test in mice. Intracerebroventricular (ICV, 1 or 2 μg/mouse) or intraperitoneal (IP, 0.5, 1, or 2 mg/kg) administration of 3α, 5α THP dose-dependently reduced the duration of immobility in Forced Swim Test without accompanying changes in ambulatory or rearing behaviors in the open-field Test. The antidepressant-like effect of 3α, 5α THP (1 μg/mouse, ICV) was potentiated by prior administration of the GABAA receptor agonist, muscimol (0.5 mg/kg, IP) and blocked by prior administration of GABAA receptor antagonist, bicuculline (1 mg/kg, IP). Administration of the agonist at diazepam binding inhibitor receptors, 4′-chlorodiazepam (4′CD, 15 mg/kg, IP) or N,N-di-n-hexyl-2-(4-fluorophenyl)-indol-3-acetamide (FGIN 1–27, 1 or 2 μg/mouse, ICV), the 11β-hydroxylase inhibitor, metyrapone (150 mg/kg, IP and 1 or 2 μg/mouse, ICV) and the selective serotonin reuptake inhibitor (SSRI), fluoxetine (20 mg/kg, IP), which are known to increase the endogenous level of neurosteroids, also reduced the duration of immobility in Forced Swim Test. The tricyclic antidepressant, imipramine (20 mg/kg, IP), which does not increase the 3α, 5α THP in the brain, also reduced the immobility time. While the antidepressant-like effect of fluoxetine, which is known to selectively increase the brain content of 3α, 5α THP, was either blocked partially by bicuculline (1 mg/kg, IP) or potentiated by muscimol (0.5 mg/kg, IP), the antidepressant-like effect of imipramine was not modified by bicuculline. These results demonstrate the antidepressant-like effect of the neurosteroid 3α, 5α THP, and suggest further evaluation for its development as a new class of antidepressant drug.
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Antidepressant-like effect of the neurosteroid 3α-hydroxy-5α-pregnan-20-one in mice Forced Swim Test
Pharmacology Biochemistry and Behavior, 2000Co-Authors: R. T. Khisti, Chandrabhan T. Chopde, Shirish P. JainAbstract:The present study aimed to examine the antidepressant-like effect of the neurosteroid 3α-hydroxy-5α-pregnan-20-one (3α, 5α THP) using the Forced Swim Test in mice. Intracerebroventricular (ICV, 1 or 2 μg/mouse) or intraperitoneal (IP, 0.5, 1, or 2 mg/kg) administration of 3α, 5α THP dose-dependently reduced the duration of immobility in Forced Swim Test without accompanying changes in ambulatory or rearing behaviors in the open-field Test. The antidepressant-like effect of 3α, 5α THP (1 μg/mouse, ICV) was potentiated by prior administration of the GABA(A) receptor agonist, muscimol (0.5 mg/kg, IP) and blocked by prior administration of GABA(A) receptor antagonist, bicuculline (1 mg/kg, IP). Administration of the agonist at diazepam binding inhibitor receptors, 4'-chlorodiazepam (4'CD, 15 mg/kg, IP) or N,N-di-n-hexyl-2-(4-fluorophenyl)-indol-3-acetamide (FGIN 1-27, 1 or 2 μg/mouse, ICV), the 11β-hydroxylase inhibitor, metyrapone (150 mg/kg, IP and 1 or 2 μg/mouse, ICV) and the selective serotonin reuptake inhibitor (SSRI), fluoxetine (20 mg/kg, IP), which are known to increase the endogenous level of neurosteroids, also reduced the duration of immobility in Forced Swim Test. The tricyclic antidepressant, imipramine (20 mg/kg, IP), which does not increase the 3α, 5α THP in the brain, also reduced the immobility time. While the antidepressant-like effect of fluoxetine, which is known to selectively increase the brain content of 3α, 5α THP, was either blocked partially by bicuculline (1 mg/kg, IP) or potentiated by muscimol (0.5 mg/kg, IP), the antidepressant-like effect of imipramine was not modified by bicuculline. These results demonstrate the antidepressant-like effect of the neurosteroid 3α, 5α THP, and suggest further evaluation for its development as a new class of antidepressant drug. (C) 2000 Elsevier Science Inc.
Irwin Lucki - One of the best experts on this subject based on the ideXlab platform.
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differential behavioral effects of the antidepressants reboxetine fluoxetine and moclobemide in a modified Forced Swim Test following chronic treatment
Psychopharmacology, 2005Co-Authors: Michelle E. Page, John F. Cryan, Irwin LuckiAbstract:Rationale The Forced Swim Test (FST) is the most widely used model for assessing potential antidepressant activity in rodents following acute or short-term treatment. However, few studies have compared the effects of short- and long-term antidepressant treatment on behaviors in the Test, despite the need to treat patients chronically to produce clinical effects.
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noradrenergic lesions differentially alter the antidepressant like effects of reboxetine in a modified Forced Swim Test
European Journal of Pharmacology, 2002Co-Authors: John F. Cryan, Michelle E. Page, Irwin LuckiAbstract:Abstract The novel antidepressant reboxetine is a selective norepinephrine reuptake inhibitor. In this study, the antidepressant-like effects of reboxetine were characterized in a modified rat Forced Swim Test. Further, in order to investigate the role of the locus coeruleus and lateral tegmental noradrenergic systems in the mediation of reboxetine's effects, the impact of different chemical lesions of these two pathways was examined on the behavioral responses induced by reboxetine in the Forced Swim Test. Reboxetine (5–20 mg/kg, s.c.) dose-dependently decreased immobility and Swimming behavior in the Forced Swim Test while it simultaneously increased climbing behavior. These effects were similar to those previously demonstrated with tricyclic antidepressants and are indicative of reboxetine's effects on the noradrenergic system. Discrete local injections of the neurotoxin 6-hydroxydopamine were employed to lesion the ventral noradrenergic bundle arising from cells located in the lateral tegmentum. This resulting lesion completely prevented reboxetine (10 mg/kg, s.c.)-induced decreases in immobility and increases in climbing behavior, demonstrating that an intact ventral noradrenergic bundle is required for the manifestation of reboxetine-induced antidepressant-like behavior in the Test. In contrast, lesions of the dorsal noradrenergic bundle which consists of neurons arising from the nucleus locus coereleus, were achieved by systemic pretreatment with the selective noradrenergic neurotoxin N -(2-chloroethyl)- N -2-bromobenzylamine (DSP-4; 50 mg/kg, i.p.). The ability of reboxetine (10 mg/kg, s.c.) to increase climbing and decrease immobility was augmented by DSP-4 pretreatment. Furthermore, neither lesions of the dorsal noradrenergic bundle nor the ventral noradrenergic bundle altered baseline immobility scores in the Forced Swim Test. Taken together, these data suggest that forebrain regions innervated by these two distinct noradrenergic pathways exert opposing influences on the behavioral response to reboxetine in the rat Forced Swim Test.
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Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified Forced Swim Test
European Journal of Pharmacology, 2002Co-Authors: John F. Cryan, Michelle E. Page, Irwin LuckiAbstract:The novel antidepressant reboxetine is a selective norepinephrine reuptake inhibitor. In this study, the antidepressant-like effects of reboxetine were characterized in a modified rat Forced Swim Test. Further, in order to investigate the role of the locus coeruleus and lateral tegmental noradrenergic systems in the mediation of reboxetine's effects, the impact of different chemical lesions of these two pathways was examined on the behavioral responses induced by reboxetine in the Forced Swim Test. Reboxetine (5 - 20 mg/kg, s.c.) dose-dependently decreased immobility and Swimming behavior in the Forced Swim Test while it simultaneously increased climbing behavior. These effects were similar to those previously demonstrated with tricyclic antidepressants and are indicative of reboxetine's effects on the noradrenergic system. Discrete local injections of the neurotoxin 6-hydroxydopamine were employed to lesion the ventral noradrenergic bundle arising from cells located in the lateral tegmentum. This resulting lesion completely prevented reboxetine (10 mg/kg, s.c.)-induced decreases in immobility and increases in climbing behavior, demonstrating that an intact ventral noradrenergic bundle is required for the manifestation of reboxetine-induced antidepressant-like behavior in the Test. In contrast, lesions of the dorsal noradrenergic bundle which consists of neurons arising from the nucleus locus coereleus, were achieved by systemic pretreatment with the selective noradrenergic neurotoxin N-(2-chloroethyl)-N-2-bromobenzylamine (DSP-4; 50 mg/kg, i.p.). The ability of reboxetine (10 mg/kg, s.c.) to increase climbing and decrease immobility was augmented by DSP-4 pretreatment. Furthermore, neither lesions of the dorsal noradrenergic bundle nor the ventral noradrenergic bundle altered baseline immobility scores in the Forced Swim Test. Taken together, these data suggest that forebrain regions innervated by these two distinct noradrenergic pathways exert opposing influences on the behavioral response to reboxetine in the rat Forced Swim Test. © 2002 Elsevier Science B.V. All rights reserved.
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antidepressant like activity of 5 ht1a agonists measured with the Forced Swim Test
Psychopharmacology, 1990Co-Authors: Scott Wieland, Irwin LuckiAbstract:This study examined the abilities of 5-hydroxytryptamine (5-HT) agonists with varying selectivity for different subtypes of 5-HT receptors to produce antidepressant-like behavioral effects in the Forced Swim Test in rats. The 5-HT1A agonists 8-OH-DPAT (0.125–1.0 mg/kg, SC) and tandospirone (SM-3997) (5–20 mg/kg, SC) both produced dose-related decreases in immobility time following subchronic treatment in rats. These effects were similar to those of the tricyclic antidepressants imipramine (5–15 mg/kg) and desipramine (5–15 mg/kg). In addition, the 5-HT1A agonists, buspirone (20 mg/kg), gepirone (20 mg/kg) and ipsapirone (10 and 20 mg/kg) demonstrated antidepressant-like effects. Other groups of rats treated subchronically with each of the 5-HT1A agonists or antidepressants showed no increase in locomotor activity, so that general changes in activity could not account for the reduction of immobility time in the Forced Swim Test. 5-HT agonists selective for other receptor subtypes, such as the 5-HT1B/1C agonistm-CPP (5 mg/kg) and the 5-HT2/1C agonist DOB (1 mg/kg), were not effective in this behavioral Test. The benzodiazepine diazepam (5 mg/kg) also failed to reduce immobility time, suggesting that anxiolytic properties of 5-HT1A agonists did not mediate this behavioral effect. A common metabolite of some of the 5-HT1A agonists, 1-PP, was ineffective in reducing immobility time. The stimulantd-amphetamine (2 mg/kg) significantly reduced immobility time but also significantly increased locomotor activity. Pretreatment with the 5-HT synthesis inhibitor PCPA alone did not alter immobility time, and did not alter the antidepressant-like effects of 8-OH-DPAT or tandospirone, suggesting that the 5-HT1A agonists are producing their antidepressant-like effects through postsynaptic 5-HT1A receptors. These results suggest that 5-HT1A agonists may have antidepressant efficacy and act as a novel class of antidepressant drug.
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Antidepressant-like activity of 5-HT1A agonists measured with the Forced Swim Test
Psychopharmacology, 1990Co-Authors: Scott Wieland, Irwin LuckiAbstract:This study examined the abilities of 5-hydroxytryptamine (5-HT) agonists with varying selectivity for different subtypes of 5-HT receptors to produce antidepressant-like behavioral effects in the Forced Swim Test in rats. The 5-HT1A agonists 8-OH-DPAT (0.125-1.0 mg/kg, SC) and tandospirone (SM-3997) (5-20 mg/kg, SC) both produced dose-related decreases in immobility time following subchronic treatment in rats. These effects were similar to those of the tricyclic antidepressants imipramine (5-15 mg/kg) and desipramine (5-15 mg/kg). In addition, the 5-HT1A agonists, buspirone (20 mg/kg), gepirone (20 mg/kg) and ipsapirone (10 and 20 mg/kg) demonstrated antidepressant-like effects. Other groups of rats treated subchronically with each of the 5-HT1A agonists or antidepressants showed no increase in locomotor activity, so that general changes in activity could not account for the reduction of immobility time in the Forced Swim Test. 5-HT agonists selective for other receptor subtypes, such as the 5-HT1B/1C agonist m-CPP (5 mg/kg) and the 5-HT2/1C agonist DOB (1 mg/kg), were not effective in this behavioral Test. The benzodiazepine diazepam (5 mg/kg) also failed to reduce immobility time, suggesting that anxiolytic properties of 5-HT1A agonists did not mediate this behavioral effect. A common metabolite of some of the 5-HT1A agonists, 1-PP, was ineffective in reducing immobility time. The stimulant d-amphetamine (2 mg/kg) significantly reduced immobility time but also significantly increased locomotor activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Cindy L. Ehlers - One of the best experts on this subject based on the ideXlab platform.
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Ontogeny and adolescent alcohol exposure in Wistar rats: open field conflict, light/dark box and Forced Swim Test
Pharmacology Biochemistry and Behavior, 2014Co-Authors: Anita Desikan, Derek N. Wills, Cindy L. EhlersAbstract:Abstract Epidemiological studies have demonstrated that heavy drinking and alcohol abuse and dependence peak during the transition between late adolescence and early adulthood. Studies in animal models have demonstrated that alcohol exposure during adolescence can cause a modification in some aspects of behavioral development, causing the “adolescent phenotype” to be retained into adulthood. However, the “adolescent phenotype” has not been studied for a number of behavioral Tests. The objective of the present study was to investigate the ontogeny of behaviors over adolescence/young adulthood in the light/dark box, open field conflict and Forced Swim Test in male Wistar rats. These data were compared to previously published data from rats that received intermittent alcohol vapor exposure during adolescence (AIE) to Test whether they retained the “adolescent phenotype” in these behavioral Tests. Three age groups of rats were Tested (post-natal day (PD) 34-42; PD55-63; PD69-77). In the light/dark box Test, younger rats escaped the light box faster than older adults, whereas AIE rats returned to the light box faster and exhibited more rears in the light than controls. In the open field conflict Test, both younger and AIE rats had shorter times to first enter the center, spent more time in the center of the field, were closer to the food, and consumed more food than controls. In the Forced Swim Test no clear developmental pattern emerged. The results of the light/dark box and the Forced Swim Test do not support the hypothesis that adolescent ethanol vapor exposure can “lock-in” all adolescent phenotypes. However, data from the open field conflict Test suggest that the adolescent and the AIE rats both engaged in more “disinhibited” and food motivated behaviors. These data suggest that, in some behavioral Tests, AIE may result in a similar form of behavioral disinhibition to what is seen in adolescence.
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Ontogeny and adolescent alcohol exposure in Wistar rats: Open field conflict, light/dark box and Forced Swim Test
Pharmacology Biochemistry and Behavior, 2014Co-Authors: Anita Desikan, Derek N. Wills, Cindy L. EhlersAbstract:Epidemiological studies have demonstrated that heavy drinking and alcohol abuse and dependence peak during the transition between late adolescence and early adulthood. Studies in animal models have demonstrated that alcohol exposure during adolescence can cause a modification in some aspects of behavioral development, causing the "adolescent phenotype" to be retained into adulthood. However, the "adolescent phenotype" has not been studied for a number of behavioral Tests. The objective of the present study was to investigate the ontogeny of behaviors over adolescence/young adulthood in the light/dark box, open field conflict and Forced Swim Test in male Wistar rats. These data were compared to previously published data from rats that received intermittent alcohol vapor exposure during adolescence (AIE) to Test whether they retained the "adolescent phenotype" in these behavioral Tests. Three age groups of rats were Tested (post-natal day (PD) 34-42; PD55-63; PD69-77). In the light/dark box Test, younger rats escaped the light box faster than older adults, whereas AIE rats returned to the light box faster and exhibited more rears in the light than controls. In the open field conflict Test, both younger and AIE rats had shorter times to first enter the center, spent more time in the center of the field, were closer to the food, and consumed more food than controls. In the Forced Swim Test no clear developmental pattern emerged. The results of the light/dark box and the Forced Swim Test do not support the hypothesis that adolescent ethanol vapor exposure can "lock-in" all adolescent phenotypes. However, data from the open field conflict Test suggest that the adolescent and the AIE rats both engaged in more "disinhibited" and food motivated behaviors. These data suggest that, in some behavioral Tests, AIE may result in a similar form of behavioral disinhibition to what is seen in adolescence. © 2014 Published by Elsevier Inc.
R. T. Khisti - One of the best experts on this subject based on the ideXlab platform.
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antidepressant like effect of the neurosteroid 3α hydroxy 5α pregnan 20 one in mice Forced Swim Test
Pharmacology Biochemistry and Behavior, 2000Co-Authors: R. T. Khisti, Chandrabhan T. Chopde, Shirish P. JainAbstract:The present study aimed to examine the antidepressant-like effect of the neurosteroid 3α-hydroxy-5α-pregnan-20-one (3α, 5α THP) using the Forced Swim Test in mice. Intracerebroventricular (ICV, 1 or 2 μg/mouse) or intraperitoneal (IP, 0.5, 1, or 2 mg/kg) administration of 3α, 5α THP dose-dependently reduced the duration of immobility in Forced Swim Test without accompanying changes in ambulatory or rearing behaviors in the open-field Test. The antidepressant-like effect of 3α, 5α THP (1 μg/mouse, ICV) was potentiated by prior administration of the GABAA receptor agonist, muscimol (0.5 mg/kg, IP) and blocked by prior administration of GABAA receptor antagonist, bicuculline (1 mg/kg, IP). Administration of the agonist at diazepam binding inhibitor receptors, 4′-chlorodiazepam (4′CD, 15 mg/kg, IP) or N,N-di-n-hexyl-2-(4-fluorophenyl)-indol-3-acetamide (FGIN 1–27, 1 or 2 μg/mouse, ICV), the 11β-hydroxylase inhibitor, metyrapone (150 mg/kg, IP and 1 or 2 μg/mouse, ICV) and the selective serotonin reuptake inhibitor (SSRI), fluoxetine (20 mg/kg, IP), which are known to increase the endogenous level of neurosteroids, also reduced the duration of immobility in Forced Swim Test. The tricyclic antidepressant, imipramine (20 mg/kg, IP), which does not increase the 3α, 5α THP in the brain, also reduced the immobility time. While the antidepressant-like effect of fluoxetine, which is known to selectively increase the brain content of 3α, 5α THP, was either blocked partially by bicuculline (1 mg/kg, IP) or potentiated by muscimol (0.5 mg/kg, IP), the antidepressant-like effect of imipramine was not modified by bicuculline. These results demonstrate the antidepressant-like effect of the neurosteroid 3α, 5α THP, and suggest further evaluation for its development as a new class of antidepressant drug.
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Antidepressant-like effect of the neurosteroid 3α-hydroxy-5α-pregnan-20-one in mice Forced Swim Test
Pharmacology Biochemistry and Behavior, 2000Co-Authors: R. T. Khisti, Chandrabhan T. Chopde, Shirish P. JainAbstract:The present study aimed to examine the antidepressant-like effect of the neurosteroid 3α-hydroxy-5α-pregnan-20-one (3α, 5α THP) using the Forced Swim Test in mice. Intracerebroventricular (ICV, 1 or 2 μg/mouse) or intraperitoneal (IP, 0.5, 1, or 2 mg/kg) administration of 3α, 5α THP dose-dependently reduced the duration of immobility in Forced Swim Test without accompanying changes in ambulatory or rearing behaviors in the open-field Test. The antidepressant-like effect of 3α, 5α THP (1 μg/mouse, ICV) was potentiated by prior administration of the GABA(A) receptor agonist, muscimol (0.5 mg/kg, IP) and blocked by prior administration of GABA(A) receptor antagonist, bicuculline (1 mg/kg, IP). Administration of the agonist at diazepam binding inhibitor receptors, 4'-chlorodiazepam (4'CD, 15 mg/kg, IP) or N,N-di-n-hexyl-2-(4-fluorophenyl)-indol-3-acetamide (FGIN 1-27, 1 or 2 μg/mouse, ICV), the 11β-hydroxylase inhibitor, metyrapone (150 mg/kg, IP and 1 or 2 μg/mouse, ICV) and the selective serotonin reuptake inhibitor (SSRI), fluoxetine (20 mg/kg, IP), which are known to increase the endogenous level of neurosteroids, also reduced the duration of immobility in Forced Swim Test. The tricyclic antidepressant, imipramine (20 mg/kg, IP), which does not increase the 3α, 5α THP in the brain, also reduced the immobility time. While the antidepressant-like effect of fluoxetine, which is known to selectively increase the brain content of 3α, 5α THP, was either blocked partially by bicuculline (1 mg/kg, IP) or potentiated by muscimol (0.5 mg/kg, IP), the antidepressant-like effect of imipramine was not modified by bicuculline. These results demonstrate the antidepressant-like effect of the neurosteroid 3α, 5α THP, and suggest further evaluation for its development as a new class of antidepressant drug. (C) 2000 Elsevier Science Inc.