title: Naltrexone suppresses ethanol intake in 6-hydroxydopamine-treated rats.
abstract: BACKGROUND
  The suppressive effect of opioid antagonists, such as naltrexone, on ethanol intake has been suggested to be based on the interference with ethanol-induced stimulation of dopamine release in the nucleus accumbens. The aim of this study was to determine whether reduction of dopamine innervation to the nucleus accumbens with the neurotoxin 6-hydroxydopamine (6-OHDA) alters naltrexone-induced suppression of ethanol consumption. Because the mesolimbic dopaminergic neurons have also been implicated in ethanol reinforcement, the effects of 6-OHDA on the maintenance and acquisition of ethanol intake were also studied.
  
  
  METHODS
  To damage accumbal terminals of the mesolimbic dopamine neurons, alcohol-preferring Alko Alcohol (AA) rats were given bilateral injections of 6-OHDA or vehicle into the nucleus accumbens after pretreatment with desipramine and pargyline. The effect of the lesion on the acquisition or maintenance of ethanol self-administration was studied in animals having continual access to ethanol solution (10% v/v) and water. Subsequently the effect of naltrexone on ethanol consumption was determined.
  
  
  RESULTS
  Naltrexone (0.03-3.0 mg/kg subcutaneously) suppressed ethanol consumption in a dose-dependent manner both in 6-OHDA-treated and control animals given a daily 90-min access to ethanol solution. When the rats had continual access to ethanol, there was a clear day-to-day decline in ethanol intake during the first 5 days of the 7-day naltrexone treatment (10 mg/kg subcutaneously). 6-OHDA treatment had no effect on either the acquisition or maintenance of ethanol self-administration. Postmortem analysis of the brain dopamine content revealed approximately 92% depletion of dopamine in the nucleus accumbens of the 6-OHDA-treated rats.
  
  
  CONCLUSIONS
  The suppressive effect of naltrexone does not depend on naltrexone's interaction with dopaminergic terminals in the nucleus accumbens. Furthermore, the role of the mesolimbic dopamine pathway is probably not central either in the acquisition or maintenance of ethanol self-administration in alcohol-preferring AA rats.
authors.affiliation: Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Koistinen
authors.forename: P
authors.initials: P
authors.lastname: Tuomainen
authors.forename: P
authors.initials: P
authors.lastname: Hyytiä
authors.forename: K
authors.initials: K
authors.lastname: Kiianmaa
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D003342:Corpus Striatum / Q000737:chemistry; D004298:Dopamine / Q000032:analysis / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009638:Norepinephrine / Q000032:analysis; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D012646:Self Administration; D012701:Serotonin / Q000032:analysis; D013565:Sympatholytics / Q000494:pharmacology*
chemical_list: D009292:Narcotic Antagonists; D013565:Sympatholytics; D012701:Serotonin; D000431:Ethanol; D009271:Naltrexone; D016627:Oxidopamine; D004298:Dopamine; D009638:Norepinephrine