期刊
JOURNAL OF NEUROCHEMISTRY
卷 86, 期 2, 页码 405-412出版社
BLACKWELL PUBLISHING LTD
DOI: 10.1046/j.1471-4159.2003.01858.x
关键词
estrogen; cocaine sensitization; D2/D3 receptors; female rat; functional autoradiography; nucleus accumbens
资金
- NCRR NIH HHS [RR11126, RR03051] Funding Source: Medline
- NINDS NIH HHS [U54 NS 39405] Funding Source: Medline
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 D-2 /D-3 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. D-2 /D-3 -stimulated [(35) S]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 [(35) S]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. [(35) S]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 D-2 /D-3 receptor activation are regulated by estrogen. These data suggest that changes in D-2 /D-3 receptor function represent one mechanism by which estrogen regulates behavioral sensitization to cocaine.
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