Naltrexone reverses ethanol-induced dopamine release in the nucleus accumbens in awake, freely moving rats.
The effect of the opioid receptor antagonist, naltrexone, on ethanol-induced changes in extracellular dopamine and serotonin in the nucleus accumbens was investigated using in vivo microdialysis in awake, freely moving rats. Locally applied ethanol (5% infused transprobe) resulted in substantial increases in dopamine in dialysate. Administration of naltrexone (cumulative dosing with 0.25-1.0 mg/kg i.p.) during ethanol administration dose-dependently reversed ethanol-induced increases in extracellular dopamine and its metabolite homovanillic acid but not serotonin. These data demonstrate an essential role for the endogenous opioid system in stimulation of dopamine release by ethanol in a brain area associated with reward and support the opioid system as a prime target for pharmacological modulation of the rewarding effects and consumption of ethanol.
Benjamin
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Center of Alcohol Studies, Rutgers University, New Brunswick, NJ 08855.
Grant
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Pohorecky
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000037:antagonists & inhibitors*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009068:Movement / Q000502:physiology; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D000431:Ethanol; D006897:Hydroxyindoleacetic Acid; D009271:Naltrexone; D004298:Dopamine