title: Autoradiographic evidence for differential G-protein coupling of 5-HT1A receptors in rat brain: lack of effect of repeated injections of fluoxetine.
abstract: The present study examined the distribution of [3H]8-OH-DPAT-labeled 5-HT1A 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-HT1A 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-HT1A 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-HT1A receptors coupled to G proteins. 5-HT1A receptor densities ranged from 7 to 63 fmol/mg tissue equivalent among hypothalamic 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 alter 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 fluoxetine-induced desensitization of hypothalamic 5-HT1A receptors is not mediated by changes in receptor density or G protein coupling.
authors.affiliation: Department of Pharmacology, Stritch School of Medicine, Loyola University Chicago, IL 60153, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Battaglia
authors.forename: L D
authors.initials: LD
authors.lastname: Van de Kar
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007267:Injections; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D005473:Fluoxetine; D019204:GTP-Binding Proteins; D006165:Guanylyl Imidodiphosphate; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors