The role of adenosine A1 receptor activation in ethanol-induced inhibition of stimulated glutamate release in the hippocampus of the fetal and adult guinea pig

The role of adenosine A₁ receptor activation in ethanol-induced inhibition of stimulated l-glutamate (Glu) release was determined in transverse hippocampal slices of the near-term fetal guinea pig and the adult guinea pig. Exposure of the slices to 48 mM ethanol inhibited K⁺-stimulated Glu efflux. Pretreatment with 8-cyclopentyltheophylline (CPT), a selective adenosine A₁ receptor antagonist, blocked the ethanol-induced inhibition of K⁺-stimulated Glu efflux in the near-term fetal and adult hippocampus. In the near-term fetus, 2-chloro-N⁶-cyclopentyladenosine (CCPA), a selective adenosine A₁ agonist, and exogenous adenosine each blocked K⁺-stimulated Glu efflux similar to that produced by 48 mM ethanol. In the adult, although K⁺ increased Glu efflux in the presence of CCPA or adenosine, the magnitude of increase was less than that of the K⁺-stimulated Glu efflux for the control condition. Exposure to ethanol alone or ethanol plus CPT produced a transient increase in endogenous adenosine efflux in the near-term fetal and adult hippocampus, which was not temporally related to the ethanol-induced inhibition of K⁺-stimulated Glu efflux. Overall, the data indicate that adenosine A₁ receptor activation mediates ethanol-induced inhibition of stimulated Glu release in the hippocampus of the near-term fetal and adult guinea pig.