Serotonergic modulation of ethanol-induced electrophysiological depressionin young and aged rats

Background: Ethanol (EtOH)-induced electrophysiological depressions in cere bellar Purkinje neurons have been shown to be potentiated by exogenously ap plied serotonin (5HT). In this study, we determined whether this modulatory action can be activated by endogenous release from presynaptic serotonergi c terminals, and whether such a response is altered by age or rat strain. Methods: Extracellular 5HT levels in cerebellar cortex were measured in rea l time by in vivo chronoamperometry, by using Nafion-coated carbon fiber el ectrodes, in anesthetized young (3-5 months old) or aged (18-24 months old) Sprague Dawley and Fischer 344 rats. Some animals were prelesioned with 5, 7 dihydroxytryptamine (5,7 DHT). Single unit electrophysiological activity was recorded from cerebellar Purkinje neurons. Serotonin or its presynaptic antagonist methiothepin was applied directly to cerebellar neurons through multibarrel pipettes. Results: Local application of methiothepin dose-dependently induced 5HT ove rflow in young Sprague Dawley and Fisher 344 rats. Methiothepin-induced 5HT release was decreased significantly in aged or 5,7 DHT-lesioned rats. Loca l application of methiothepin or 5HT potentiated EtOH-induced electrophysio logical depression of Purkinje neurons in young animals of both strains. Me thiothepin-potentiated, EtOH-elicited neuronal inhibition was reduced great ly in aged or 5,7 DHT-lesioned rats. Serotonin-facilitated EtOH responses w ere reduced in the aged Sprague Dawley rats. Conclusions: EtOH-induced electrophysiological responses in cerebellum can be facilitated by endogenous 5HT release by using a 5HT autoreceptor antago nist. Such actions are attenuated in aged rats perhaps through a presynapti c serotonergic mechanism.