Alterations in mesolimbic dopamine function during the abstinence period following chronic ethanol consumption.
Previous work demonstrated that the locomotor stimulant actions of amphetamine, cocaine and nicotine were increased when these drugs were given during the abstinence phase after chronic ethanol consumption. These changes were seen at 6 days and at 2 months after cessation of alcohol. The present study examined neuronal alterations which might be related to these changes in behaviour. Markedly reduced spontaneous firing rates of dopaminergic cells in the ventral tegmental area (VTA) in midbrain slices were seen 6 days into the abstinence period after cessation of chronic ethanol consumption, but by 2 months the firing rates had returned to control values. Increased affinity of striatal receptors for the D1-like receptor ligand 3H-SCH23390, but no change in the receptor density, was found both at the 6 day and the 2 month intervals. The binding properties of striatal D2-like receptors, of D1-like and D2-like receptors in the frontal cerebral cortex, and the release of tritiated dopamine from slices of striatum or frontal cerebral cortex, were unchanged at 6 days and 2 months. It is suggested that the decreased neuronal firing leads to a persistent increase in sensitivity of D1-like receptors and that these changes could explain the increased effects of the other drugs of abuse.
Bailey
C P
CP
Drug Dependence Unit, Department of Psychology, University of Durham, South Road, DH1 3LE, Durham, UK.
O'Callaghan
M J
MJ
Croft
A P
AP
Manley
S J
SJ
Little
H J
HJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000428:Alcohol Drinking / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology; D008032:Limbic System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D011954:Receptors, Dopamine / Q000502:physiology; D013695:Temperance; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
D002492:Central Nervous System Depressants; D011954:Receptors, Dopamine; D000431:Ethanol; D004298:Dopamine