Estrogen-dependent alterations in D2/D3-induced G protein activation in cocaine-sensitized female rats
Article first published online: 4 FEB 2004
Journal of Neurochemistry
Volume 86, Issue 2, pages 405–412, July 2003
How to Cite
Febo, M., González-Rodríguez, L. A., Capó-Ramos, D. E., González-Segarra, N. Y. and Segarra, A. C. (2003), Estrogen-dependent alterations in D2/D3-induced G protein activation in cocaine-sensitized female rats. Journal of Neurochemistry, 86: 405–412. doi: 10.1046/j.1471-4159.2003.01858.x
- Issue published online: 4 FEB 2004
- Article first published online: 4 FEB 2004
- Received February 11, 2003; revised manuscript received April 7, 2003; accepted April 15, 2003.
- cocaine sensitization;
- D2/D3 receptors;
- female rat;
- functional autoradiography;
- nucleus accumbens
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′-(γ-thio) triphosphate (GTPγS) 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]GTPγS 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]GTPγS 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.