Estrogen-dependent alterations in D2/D3-induced G protein activation in cocaine-sensitized female rats.
Enviado por Annabell Segarra el
Título | Estrogen-dependent alterations in D2/D3-induced G protein activation in cocaine-sensitized female rats. |
Publication Type | Journal Article |
Year of Publication | 2003 |
Autores | Febo, MA, González-Rodríguez, LA, Capó-Ramos, DE, González-Segarra, NY, Segarra, AC |
Journal | J Neurochem |
Volume | 86 |
Issue | 2 |
Pagination | 405-12 |
Date Published | 2003 Jul |
ISSN | 0022-3042 |
Palabras clave | Animals, Autoradiography, Behavior, Animal, Binding, Competitive, Brain, Cocaine, Dopamine Agonists, Dopamine Uptake Inhibitors, Drug Administration Schedule, Drug Implants, Estradiol, Estrogens, Female, GTP-Binding Proteins, Guanosine 5'-O-(3-Thiotriphosphate), Ovariectomy, Quinpirole, Rats, Rats, Sprague-Dawley, Receptors, Dopamine D2, Receptors, Dopamine D3, Reward, Sulfur Radioisotopes |
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. |
Alternate Journal | J. Neurochem. |
PubMed ID | 12871581 |
Grant List | RR03051 / RR / NCRR NIH HHS / United States RR11126 / RR / NCRR NIH HHS / United States U54 NS 39405 / NS / NINDS NIH HHS / United States |