Chronic ethanol administration alters activity in ventral tegmental area neurons after cessation of withdrawal hyperexcitability.
The present study investigated the activity of neurons in the mesolimbic dopamine system after the end of the acute phase of the behavioural signs of ethanol withdrawal in mice. This was designed to provide a comparison with earlier behavioural studies, in which greater development of sensitisation to amphetamine and cocaine, but no change in the initial effects of these compounds, or in the behaviour in the absence of drug treatment, was seen when repeated injection of these psychostimulants were given after chronic ethanol consumption. In the present study, single unit recordings were made from dopamine-sensitive neurons in the ventral tegmental area in perfused midbrain slices prepared 24 h after cessation of chronic ethanol consumption. Profound decreases in firing of the ventral tegmental area (VTA) neurons were seen in slices prepared after the ethanol treatment. Firing rates increased after application of N-methyl-dl-aspartate, but still remained lower and more variable after the ethanol treatment. Application of dopamine or amphetamine, following stimulation of firing with a low concentration of N-methyl-dl-aspartate, also resulted in lower firing rates in slices from ethanol-treated mice. No changes were seen in release of tritiated dopamine, in response to applied KCl or amphetamine, from slices of striatum or cerebral cortex, prepared 24 h after cessation of the chronic ethanol consumption, compared with control values. The results demonstrate that very substantial decreases in firing rate, and in the number of active cells, occur in VTA neurons at a time when withdrawal hyperexcitability was no longer apparent and overt changes in behaviour were not seen.
Bailey
C P
CP
Drug Dependence Unit, Psychology Department, Durham University, South Road, Durham DH1 3LE, UK.
Manley
S J
SJ
Watson
W P
WP
Wonnacott
S
S
Molleman
A
A
Little
H J
HJ
D000200:Action Potentials / Q000187:drug effects; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D006948:Hyperkinesis / Q000139:chemically induced*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D011189:Potassium Chloride / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D000431:Ethanol; D016202:N-Methylaspartate; D011189:Potassium Chloride; D000661:Amphetamine; C083705:N-methyl-DL-aspartic acid; D004298:Dopamine