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.