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]GTPgammaS 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 degrees C for subsequent cryosectioning. In vitro functional autoradiography was performed using baclofen (300 microM), a GABA(B) receptor agonist, to stimulate [(35)S]GTPgammaS binding in tissue sections at the level of the ventral tegmental area (VTA). OVX-EB rats showed lower levels of [(35)S]GTPgammaS 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]GTPgammaS 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.
Laboratory of Neuroendocrinology, Department of Physiology andZ Biophysics, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico 00936-5067.
Marcelo
M
Febo
Annabell C
AC
Segarra
D000818:Animals; D001345:Autoradiography; D001418:Baclofen / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D018728:Entorhinal Cortex / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D018755:GABA Agonists / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D004967:Estrogens; D018755:GABA Agonists; D018080:Receptors, GABA-B; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D005680:gamma-Aminobutyric Acid; D019204:GTP-Binding Proteins; D001418:Baclofen; D003042:Cocaine