Autoradiographic evidence for differential G-protein coupling of 5- HT(1A) receptors in rat brain: Lack of effect of repeated injections of fluoxetine

The present study examined the distribution of [³H]8-OH-DPAT-labeled 5- HT(1A) receptors and their degree of coupling to G proteins in the hypothalamus and several other brain regions. In addition, we also investigated the effects of repeated injections of fluoxetine on the density and G protein coupling of 5-HT(1A) receptors in hypothalamic nuclei and other brain regions using autoradiography. Male rats received daily injections of either fluoxetine (10 mg/kg, ip) for 3, 7, 14, and 22 days, or saline for 22 days. 5-HT(1A) receptors were labeled by 2 nM [³H]8-hydroxy-2- (dipropylamino)tetralin ([³H]-8-OH-DPAT) in the absence or presence of guanylylimidodiphosphate (Gpp(NH)p, 10^-5 M) to determine the percentage of 5-HT(1A) receptors coupled to G proteins. 5-HT(1A) receptor densities ranged from 7 to 63 fmol/mg tissue equivalent among hypothalamic nuclei. Similarly, the degree of G protein coupling to 5-HT(1A) receptors varied markedly among hypothalamic nuclei (from 14% to 61%) and among other brain regions (from 17% to 85%). Fluoxetine did not alter the density or the degree of coupling of 5- HT(1A) receptors in any brain regions. These data indicate marked regional differences in the degree of G protein-coupled 5-HT(1A) receptors and suggest that fluoxetine-induced desensitization of hypothalamic 5-HT(1A) receptors is not mediated by changes in receptor density or G protein coupling.