Ethanol has been shown to affect several transmitter- and voltage-gated channels in the brain, although little attention has focused on potential interactions between ethanol and metabotropic glutamate receptors (mGluRs). This is of interest as mGluRs are now recognized to be important components of synaptically mediated responses, including short- and long-term changes in the efficacy of neurotransmission. Cerebellar Purkinje neurons are sensitive to the effects of ethanol and express high levels of mGluRs. We made extracellular recordings from cerebellar Purkinje neurons at 21-37 days in culture to examine the effect of ethanol on mGluR-mediated responses. mGluRs were activated by pressure ejection of 300 microM (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), a selective agonist of mGluRs, or 5 microM quisqualate (Quis). As Quis activates both ionotropic and metabotropic glutamate receptors, 50 microM 6,7-dinitroquinoxaline-2,3-dione (DNQX) was used to block the ionotropic component of Quis-mediated responses. Both ACPD and Quis produced biphasic changes in firing rates consisting of an initial brief excitatory phase (5-20 s) followed by a prolonged inhibitory phase (10 s to 2.5 min), and induced the generation of bursts. Addition of 33 mM (150 mg%) ethanol to the recording medium had little effect on ACPD-mediated responses. In the presence of 66 mM (300 mg%) ethanol, however, ACPD-mediated responses exhibited an increase in the total response duration, with no change in the percent excitation or the induction of bursts as compared to controls. On the other hand, 66 mM ethanol decreased Quis-induced burst activity, while having no effect on the percent excitation or the total response duration.(ABSTRACT TRUNCATED AT 250 WORDS)