Anxiolytic action of a neurokinin1 receptor antagonist in the social interaction test.
CGP 49823, a substance P antagonist acting at NK1 receptors, had significant anxiolytic effects at 3, 10 and 30 mg/kg orally in the high-light unfamiliar and low-light unfamiliar conditions of the social interaction test but was without effect in the low-light familiar condition. The effects were less marked after 3 and 6 weeks of treatment (10 mg/kg/day), indicating that some tolerance had developed, but a significant anxiolytic effect still remained. After 3 weeks of diazepam treatment (2 mg/kg/day, intraperitoneally), tolerance developed to the anxiolytic effects, and there was an anxiogenic response 24 h after withdrawal. In contrast, there were no anxiogenic withdrawal effects 24 h after 3 weeks or 24, 48 or 72 h after 6 weeks treatment with CGP 49823 (10 mg/kg/day). These results suggest that the compound may prove to be a useful anxiolytic and that substance P may play a role in mediating states of anxiety.
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Psychopharmacology Research Unit, UMDS, Guy's Hospital, London, United Kingdom. s.file@umds.ac.uk
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004361:Drug Tolerance; D006234:Handling, Psychological; D007398:Interpersonal Relations; D008029:Lighting; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D013315:Stress, Psychological / Q000523:psychology
D014151:Anti-Anxiety Agents; C110064:CGP 49823; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011804:Quinolines; D003975:Diazepam