Focal application of alcohols elevates extracellular dopamine in rat brain: a microdialysis study.
Dopaminergic systems are thought to play a major role in the stimulant and reinforcing properties of drugs of abuse, including ethanol. The present study describes the effects of local perfusion with ethanol (and other alcohols) on extracellular dopamine in the striatum and nucleus accumbens. Following the establishment of basal dopamine levels (2-3 h), various concentrations of ethanol in artificial CSF (0.01-10% v/v) were slowly perfused through a microdialysis probe. Each dose of ethanol was found to increase dopamine concentrations in both the striatum and nucleus accumbens. This increase was dose-related in the striatum. The exclusion of calcium and inclusion of 12.5 mM magnesium in the perfusion medium prevented, or greatly attenuated the ethanol-induced dopamine (DA) release. Thus, the release of DA by ethanol is exocytotic in nature and involves calcium-dependent processes. The other alcohols tested, namely methanol and butanol, demonstrated a structure-activity relationship together with ethanol, in their ability to increase extracellular DA. The relative potency was butanol greater than ethanol greater than methanol. The diffusion of ethanol into the brain tissue was investigated following perfusion through the probe. Relatively low concentrations of ethanol were found in striatal tissue during perfusion and they declined rapidly with time, following the removal of ethanol from the perfusate. The concentrations of ethanol achieved in brain tissue following focal application through the microdialysis probe were relevant to human intoxication.
Wozniak
K M
KM
Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
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Mele
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Linnoila
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D000818:Animals; D000440:Butanols / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D000432:Methanol / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000440:Butanols; D000431:Ethanol; D004298:Dopamine; D000432:Methanol