DISSOCIATION OF EFFECTS OF CHRONIC DIAZEPAM TREATMENT AND WITHDRAWAL ON HIPPOCAMPAL DIALYSATE 5-HT AND MCPP-INDUCED ANXIETY IN RATS

Acute (10 mg/kg, i.p.) and chronic (10 mg/kg/day, i.p. for 10 days) di azepam treatments decreased hippocampal dialysate 5-HT (but not 5-HIAA ) concentrations in freely moving rats, suggesting decreased availabil ity of 5-HT to receptors. Twenty-four hours after the last chronic dia zepam injection, hippocampal dialysate 5-HT did not differ from that i n vehicle-treated rats. However, although reduced 5-HT availability of ten increases postsynaptic 5-HT receptor-mediated responses, the anxio genic effect of m-chlorophenylpiperazine (mCPP), which is mediated by the activation of postsynaptic 5-HT2C receptors, was not increased (as indicated by the elevated plus-maze test) when given 2 days after 10 days of chronic diazepam, in intact rats. Nevertheless, concurrently i n that test, significantly increased anxiety occurred after withdrawal from chronic diazepam (10 mg/kg/day x 10 days). The results suggest t hat benzodiazepine withdrawal-induced anxiety Is not mediated by chang es in 5-HT2C receptor sensitivity, and may be independent of the benzo diazepine-induced reduction of 5-HT release in the rat hippocampus.