Alcohol-withdrawn animals have a prolonged increase in dopamine D2high receptors, reversed by general anesthesia: relation to relapse?
The biochemical basis for alcohol addiction and relapse is not known. Although ethanol promotes the release of dopamine like other drugs of abuse, many unknown factors remain to be investigated concerning the biochemical abnormalities which persist after ethanol drinking and which contribute to alcohol relapse. Although ethanol withdrawal is associated with enhanced sensitivity to dopamine in animals and humans, only minor changes in the striatal density of dopamine D2 receptors have been found in humans, and animals show a small reduction in striatal D2 receptors. But how can dopamine-related functions be increased in ethanol withdrawal in the face of an unchanged or reduced density of dopamine D2 receptors? Considering that ethanol sensitizes rats to amphetamine, and that the high-affinity state of D2, or D2High, is markedly increased in striata from amphetamine-sensitized rats, we measured the density of D2High in striata from rats withdrawn from ethanol. These sites were elevated by 360% (7.2 pmol/g) for at least 8 days after stopping ethanol and returned to normal levels of 2 pmol/g after 2 weeks of ethanol withdrawal. In addition, 1 h of deep general anesthesia given 5 days into withdrawal resulted in a normal level of D2High within 24 h. Because the D2High states are the functional form of D2, their elevated density in ethanol withdrawal may be related to ethanol relapse in humans. General anesthesia may alleviate aspects of alcohol or amphetamine abuse or psychosis associated with elevated D2High.
Seeman
Philip
P
Department of Pharmacology, University of Toronto, Medical Science Building, Toronto, Ontario M5S 1A8, Canada. philip.seeman@utoronto.ca
Tallerico
Teresa
T
Ko
Françoise
F
D000768:Anesthesia, General / Q000379:methods; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis*; D055502:Secondary Prevention; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D013997:Time Factors
D017448:Receptors, Dopamine D2; D000431:Ethanol