Subchronic fluoxetine administration to rats: effects on 5-HT autoreceptor activity as measured by in vivo...

Subchronic administration of fluoxetine to rats has been shown to induce subsensitivity of presynaptic 5-HT(1A) and 5-HT(1B) autoreceptors, and also postsynaptic 5-HT(1A) receptors in the hypothalamus. We investigated the effects of administration of fluoxetine (10 mg/kg i.p.) to rats for 6 days on presynaptic 5-HT(1A) receptor activity in the hypothalamus, postsynaptic 5-HT(1A) receptor activity in the hippocampus, and presynaptic 5-HT(1B) autoreceptor activity in both areas, using in vivo microdialysis. The effect of the 5-HT(1B/1D) antagonist (N-[4-methoxy-3-(4-methyl-1-piperizinyl)phenyl]-2'-methyl-4'-(5- methyl-1,2,4-oxadiazole-3-yl)[1,1'-biphenyl]-carboxamide (GR 127935) (5 mg/kg s.c.) to elevate 5-hydroxytryptamine (5-HT) levels was reduced in hippocampus but not hypothalamus of fluoxetine-treated rats. Fluoxetine did not alter either presynaptic 5-HT(1A) autoreceptor activity, as measured by the effect of injection of 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) (0.2 mg/kg or 50 microg/kg s.c.) on 5-HT levels in the hypothalamus, or postsynaptic 5-HT(1A) receptor activity, as measured by the effect of 8-OH-DPAT (0.2 mg/kg s.c.) on cyclic AMP accumulation, in the hippocampus.