The role of opioid-dopamine interactions in the induction and maintenance of ethanol consumption.
1. Alcohol is one of the most widely used recreational drugs, but also one of the most widely abused, causing vast economic, social and personal damage. 2. Several animal models are available to study the reinforcing mechanisms that are the basis of the abuse liability of ethanol. Innate differences in opioid or dopamine neurotransmission may enhance the abuse liability of ethanol, as indicated by animal and human studies. 3. Opioid antagonists have been shown to be effective, both experimentally and clinically, in decreasing ethanol consumption, presumably since ethanol induces the release of endogenous opioid peptides in vivo. However, ethanol may also stimulate the formation of opiate-like compounds, which could interact with opioid (or dopamine) receptors. Ethanol may cause changes in neurotransmission mediated via opioid receptors that determines whether alcohol abuse is more or less likely. 4. Ethanol appears to facilitate dopamine release by increasing opioidergic activity, disinhibiting dopaminergic neurons (by inhibition of GABAergic neurotransmission) via mu-opioid receptors in the ventral tegmental area (VTA) and delta-opioid receptors in the nucleus accumbens (NAcc). The effects of ethanol would be antagonised by presynaptic kappa-opioid receptors present on dopaminergic terminals in the NAcc. 5. Mesolimbic dopamine release induced by ethanol consumption seems to indicate ethanol-related stimuli are important, focussing attention on and enabling learning of the stimuli. However, studies indicate that there are redundant pathways, and neural pathways 'downstream' of the mesolimbic dopamine system, which also enable the reinforcing properties of ethanol to be mediated.
Cowen
M S
MS
Dept. of Pharmacology, Monash University, Clayton, Vic., Australia.
Lawrence
A J
AJ
D000428:Alcohol Drinking; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009294:Narcotics / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051381:Rats
D009294:Narcotics; D018377:Neurotransmitter Agents; D004298:Dopamine