Tolerance to the behavioural effect of serotonergic (5-HT1B) agonists in the isolation-induced social behavioural deficit test.
In mice, isolation-induced social behavioural deficits are attenuated by stimulants of 5-HT1B receptors, such as TFMPP or CGS 120 66B. Repeated treatment with RU 24969 (5 mg/kg, daily, for 3 days) reduced the effect of TFMPP and that of other 5-HT1B agonists (CGS 120 66B, m-CPP, RU 24969). Similarly, repeated treatment with CGS 120 66B (8 mg/kg, twice a day for 3 days) abolished the effect of a test-dose of the same drug. Desensitization of the 5-HT1B receptors involved in this effect is suggested to have occurred. Such a desensitization may be therapeutically relevant, since acute administration of benzodiazepines and chronic administration of antidepressants both reversed the effect of TFMPP.
Frances
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Département de Pharmacologie, INSERM U.302, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Monier
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004361:Drug Tolerance; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000502:physiology*; D012934:Social Isolation
D007211:Indoles; D010879:Piperazines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C052561:CGS 12066B; C018406:1-(3-trifluoromethylphenyl)piperazine; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid