Dissociation of effects of chronic diazepam treatment and withdrawal on hippocampal dialysate 5-HT and mCPP-induced anxiety in rats.
Acute (10mg/kg, i.p.) and chronic (10mg/kg/day, i.p. for 10 days) diazepam treatments decreased hippocampal dialysate 5-HT (but not 5-HIAA) concentrations in freely moving rats, suggesting decreased availability of 5-HT to receptors. Twenty-four hours after the last chronic diazepam injection, hippocampal dialysate 5-HT did not differ from that in vehicle-treated rats. However, although reduced 5-HT availability often increases postsynaptic 5-HT receptor-mediated responses, the anxiogenic effect of m-chlorophenylpiperazine (mCPP), which is mediated by the activation of postsynaptic 5-HT(2C) 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 in that test, significantly increased anxiety occurred after withdrawal from chronic diazepam (10mg/kg/day x 10 days). The results suggest that benzodiazepine withdrawal-induced anxiety is not mediated by changes in 5-HT(2C) receptor sensitivity, and may be independent of the benzodiazepine-induced reduction of 5-HT release in the rat hippocampus.
Gibson
E.L.
EL
Department of Neurochemistry, Institute of Neurology, 1 Wakefield Street, London, WC1N 1PJ, UK.
Barnfield
A.M.C.
AM
Curzon
G.
G