Serotonergic modulation of ethanol-induced electrophysiological depression in young and aged rats.
BACKGROUND
Ethanol (EtOH)-induced electrophysiological depressions in cerebellar Purkinje neurons have been shown to be potentiated by exogenously applied serotonin (5HT). In this study, we determined whether this modulatory action can be activated by endogenous release from presynaptic serotonergic terminals, and whether such a response is altered by age or rat strain.


METHODS
Extracellular 5HT levels in cerebellar cortex were measured in real time by in vivo chronoamperometry, by using Nafion-coated carbon fiber electrodes, 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 overflow in young Sprague Dawley and Fisher 344 rats. Methiothepin-induced 5HT release was decreased significantly in aged or 5,7 DHT-lesioned rats. Local application of methiothepin or 5HT potentiated EtOH-induced electrophysiological depression of Purkinje neurons in young animals of both strains. Methiothepin-potentiated, EtOH-elicited neuronal inhibition was reduced greatly in aged or 5,7 DHT-lesioned rats. Serotonin-facilitated EtOH responses were 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 antagonist. Such actions are attenuated in aged rats perhaps through a presynaptic serotonergic mechanism.
Jeng
C H
CH
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.
Chou
J R
JR
Hoffer
B J
BJ
Wang
Y
Y
D015116:5,7-Dihydroxytryptamine; D000367:Age Factors; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D018490:Serotonin Agents; D012702:Serotonin Antagonists / Q000494:pharmacology
D002492:Central Nervous System Depressants; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D000431:Ethanol; D008719:Methiothepin