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Title: | A novel 5-HT2A receptor antagonist exhibits antidepressant-like effects in a battery of rodent behavioural assays: Approaching early-onset antidepressants |
Authors: | Mahesh, R. |
Keywords: | Pharmacy Antidepressant Hyperemotionality |
Issue Date: | Jan-2010 |
Publisher: | Elsevier |
Abstract: | Collective evidence suggests that inhibition of neuronal 5-hydroxytryptamine type 2A (5-HT2A) receptors contributes to the assuagement of depression-like behaviour in rodents. The present study evaluated the antidepressant-like effect of the 5-((4-benzo [α] isothiazol-3-yl) piperazin-1-yl) methyl)-6-chloroindolin-2-one (BIP-1), a compound having affinity to 5-HT2A receptors, using a rodent behavioural test battery. Acute BIP-1 (0.25–4 mg/kg) pretreatment reduced the quipazine-induced head twitches in mice and produced antidepressant-like effects in mouse forced swim and tail suspension tests. BIP-1 reversed the depressogenic-like effects of meta-chlorophenyl piperazine and augmented the antidepressant-like effects of amitryptiline and harmane. Chronic (14 days) treatment with BIP-1 (1 and 2 mg/kg) or amitriptyline (10 mg/kg) alleviated the behavioural anomalies of olfactory bulbectomised rats in modified open field exploration, social interaction, hyperemotionality and sucrose preference paradigms. When BIP-1 treatment was combined with amitryptyline, a short duration regimen (7 days) was sufficient to reverse the bulbectomy induced anomalies. This investigation revealed that 5-HT2A receptor antagonism is the principal mechanism behind the antidepressant-like effects of BIP-1. Finally, we propound the combination of 5-HT2A receptor antagonists and tricyclic antidepressants as a likely strategy to achieve an early-onset of antidepressant action. |
URI: | https://www.sciencedirect.com/science/article/abs/pii/S0091305709002871 http://dspace.bits-pilani.ac.in:8080/xmlui/handle/123456789/13144 |
Appears in Collections: | Department of Pharmacy |
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