Cocaine alters GABA B ‐mediated G‐protein activation in the ventral tegmental area of female rats: Modulation by estrogen

In female rats, estrogen has been reported to enhance cocaine sensitization. Here we investigated the effect of estrogen and cocaine treatments on GABA B ‐stimulated [ 35 S]GTPγS binding. Ovariectomized rats without (OVX) and with estrogen treatment (OVX‐EB) were pretreated with saline or cocaine (15 mg/kg, i.p.) for 5 days and after 1 week of withdrawal challenged with cocaine. One hour after the final injection, animals were sacrificed, brains immediately frozen, and stored at −70°C for subsequent cryosectioning. In vitro functional autoradiography was performed using baclofen (300 μM), a GABA B receptor agonist, to stimulate [ 35 S]GTPγS binding in tissue sections at the level of the ventral tegmental area (VTA). OVX‐EB rats showed lower levels of [ 35 S]GTPγS binding in the VTA (−15%) and entorhinal cortex (EC) (−60%). The effect of cocaine on GABA B ‐mediated G‐protein activation varied with the presence of estrogen. Repeated cocaine administration reduced [ 35 S]GTPγS binding in the VTA and EC of OVX rats and increased it in OVX‐EB. Thus, our data suggest that estrogen reduces GABA B ‐mediated G‐protein activation in female rats. The results also show that estrogen strongly influences cocaine‐induced alterations in GABA B function in the VTA and EC of female rats. Synapse 54:30–36, 2004. © 2004 Wiley‐Liss, Inc.