Ethanol inhibits the uptake of exogenous norepinephrine from the extracellular space of the rat cerebellum

Abstract

Rapid chronoamperometric recordings using nafion-coated carbon fiber electrodes coupled with pressure-ejection of drugs were used to investigate the effects of ethanol on norepinephrine (NE)-containing nerve terminals in the urethane-anesthetized Fischer 344 rat. Local application of ethanol from a double-barrel micropipette did not produce detectable changes in extracellular levels of NE in the rat cerebellar cortex. However, when ethanol was applied prior to local application of NE, it was seen to inhibit the uptake of NE from the extracellular space. These results were compared to the effects seen from the local application of a known high-affinity uptake inhibitor, nomifensine. Nomifensine was found to inhibit the extracellular uptake of NE in rat cerebeller cortex similar to ethanol. Our results support the hypothesis that one effect of ethanol on the noradrenergic system of the rat cerebellum is an alteration in the uptake of NE into NE-containing nerve endings. In addition, the present data concerning ethanol-induced inhibition of NE clearance or uptake support our previous electrophysiological studies in which we found that ethanol can potentiate the modulatory effects of β-agonists on GABA responses of cerebellar Purkinje neurons.