title: Central administration of an opiate antagonist decreases oral ethanol self-administration in rats.
abstract: BACKGROUND
  Opioid peptides have been implicated in various behavioral actions of alcohol, including its reinforcing effects; however, the role of specific brain sites for these actions remains to be explored. The present study examined the effects of intracerebroventricular (ICV) or intracerebral injections of an opiate antagonist (methylnaloxonium) on ethanol self-administration. The nucleus accumbens and amygdala were selected as intracerebral sites because these regions have been implicated in the reinforcing effects of drugs of abuse.
  
  
  METHODS
  Male Wistar rats were trained in a limited-access paradigm (30 min/day) to respond for ethanol (10% w/v) or water in a two-lever free-choice condition using a saccharin fading procedure. After the establishment of stable baseline responding for ethanol, animals were implanted stereotaxically with a guide cannula above the lateral ventricle or with bilateral guide cannulae either above the nucleus accumbens or amygdala. After postoperative recovery of stable baseline responding, the rats were tested 15 min after ICV or intracerebral microinjections of methylnaloxonium (0-2000 ng).
  
  
  RESULTS
  Injections of methylnaloxonium into the amygdala significantly reduced responding for ethanol at doses of 250-500 ng. Injections of methylnaloxonium into the nucleus accumbens significantly reduced responding for ethanol at doses of 500-1000 ng, whereas higher doses were needed ICV.
  
  
  CONCLUSIONS
  These results provide evidence that opioid receptors located in the amygdala and nucleus accumbens may be involved in the regulation of ethanol self-administration.
authors.affiliation: Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Heyser
authors.forename: A J
authors.initials: AJ
authors.lastname: Roberts
authors.forename: G
authors.initials: G
authors.lastname: Schulteis
authors.forename: G F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000679:Amygdala / Q000187:drug effects; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D002492:Central Nervous System Depressants; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; D009270:Naloxone; D000431:Ethanol; C041269:N-methylnaloxone