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.
Febo
Marcelo
M
Laboratory of Neuroendocrinology, Department of Physiology andZ Biophysics, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico 00936-5067.
Segarra
Annabell C
AC
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