title: Estrogen-dependent alterations in D2/D3-induced G protein activation in cocaine-sensitized female rats.
abstract: Estrogen potentiates behavioral sensitization to cocaine in the female rat by mechanisms that remain undetermined. In this study, functional receptor autoradiography was used to investigate estrogen modulation of D2/D3 receptor-induced G protein activation in components of the reward pathway of female rats treated acutely and repeatedly with cocaine. Rats were ovariectomized and given an empty (OVX group) or estradiol benzoate-filled (OVX-EB group) implant. After a week, animals received a daily saline or cocaine injection (15 mg/kg, i.p.) for 5 days, and again on day 13. Animals were killed, and brains were removed and cryosectioned. D2/D3-stimulated [35S]guanosine 5'-(gamma-thio) triphosphate (GTPgammaS) binding was assessed in the cingulate cortex area 2 (Cg2), striatum (STR), nucleus accumbens (NAc) and ventral tegmental area (VTA). OVX-EB rats showed more [35S]GTPgammaS binding in the Cg2 and lower binding in the VTA than OVX rats; in the VTA this effect was reversed by a single cocaine injection. Repeated cocaine administration had opposite effects in OVX and OVX-EB rats. [35S]GTPgammaS binding was decreased in the Cg2, NAc and STR of OVX-EB rats, and increased in OVX rats. The present results support the hypothesis that cocaine-induced changes in D2/D3 receptor activation are regulated by estrogen. These data suggest that changes in D2/D3 receptor function represent one mechanism by which estrogen regulates behavioral sensitization to cocaine.
authors.affiliation: Laboratory of Neuroendocrinology, Department of Physiology, University of Puerto Rico, School of Medicine, San Juan, Puerto Rico.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Febo
authors.forename: Loida A
authors.initials: LA
authors.lastname: González-Rodríguez
authors.forename: David E
authors.initials: DE
authors.lastname: Capó-Ramos
authors.forename: Naggai Y
authors.initials: NY
authors.lastname: González-Segarra
authors.forename: Annabell C
authors.initials: AC
authors.lastname: Segarra
mesh_terms: D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004334:Drug Administration Schedule; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D010052:Ovariectomy; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D012201:Reward; D013462:Sulfur Radioisotopes
chemical_list: D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; C493595:Drd3 protein, rat; D004343:Drug Implants; D004967:Estrogens; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013462:Sulfur Radioisotopes; C074283:estradiol 3-benzoate; D019257:Quinpirole; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004958:Estradiol; D019204:GTP-Binding Proteins; D003042:Cocaine