AUTORADIOGRAPHIC EVIDENCE FOR DIFFERENTIAL G-PROTEIN COUPLING OF 5-HT1A RECEPTORS IN RAT-BRAIN - LACK OF EFFECT OF REPEATED INJECTIONS OF FLUOXETINE

The present study examined the distribution of [H-3]8-OH-DPAT-labeled 5-HT1A receptors and their degree of coupling to G proteins in the hyp othalamus and several other brain regions. In addition, we also invest igated the effects of repeated injections of fluoxetine on the density and G protein coupling of 5-HT1A receptors in hypothalamic nuclei and other brain regions using autoradiography. Male rats received daily i njections of either fluoxetine (10 mg/kg, ip) for 3, 7, 14 and 22 days , or saline for 22 days. 5-HT1A receptors were labeled by 2 nM [H-3]8- hydroxy-2-(dipropylamino)tetralin ([H-3]8-OH-DPAT) in the absence or p resence of guanylylimidodiphosphate (Gpp(NH)p, 10(-5) M) to determine the percentage of 5-HT1A receptors coupled to G proteins. 5-HT1A recep tor densities ranged from 7 to 63 fmol/mg tissue equivalent among hypo thalamic nuclei. Similarly, the degree of G protein coupling to 5-HT1A receptors varied markedly among hypothalamic nuclei (from 14% to 61%) and among other brain regions (from 17% to 85%). Fluoxetine did not a lter the density or the degree of coupling of 5-HT1A receptors in any brain regions. These data indicate marked regional differences in the degree of G protein-coupled 5-HT1A receptors and suggest that fluoxeti ne-induced desensitization of hypothalamic 5-HT1A receptors is not med iated by changes in receptor density or G protein coupling. (C) 1997 E lsevier Science B.V.