title: Effects of chronic binge-like ethanol consumption on cocaine self-administration in rhesus monkeys.
abstract: BACKGROUND
  Most cocaine abusers also abuse alcohol, but little is known about interactions that promote co-abuse. These experiments in rhesus monkeys determined the effects of >8 weeks of ethanol (EtOH) consumption on cocaine self-administration (n=6), effects of dopamine (DA) receptor antagonists on cocaine reinforcement (n=3-4 per drug) and the ability of the D2-like DA receptor agonist quinpirole to elicit yawning (n=3).
  
  
  METHODS
  Monkeys self-administered cocaine (0.0-1.0mg/kg/injection, i.v.) under a 300-s fixed-interval schedule and the above-listed variables were measured before EtOH exposure. Next, monkeys consumed a sweetened, 4% EtOH solution in the home cage under binge-like conditions: 1h, 5 days/week with daily intake equaling 2.0g/kg EtOH. After approximately 8 weeks, measures were re-determined, then EtOH drinking was discontinued. Finally, acute effects of EtOH on cocaine self-administration were determined by infusing EtOH (0.0-1.0g/kg. i.v.) prior to cocaine self-administration sessions (n=4).
  
  
  RESULTS
  In five of six monkeys, EtOH drinking increased self-administration of low cocaine doses but did not alter reinforcing effects of higher doses. Self-administration returned to baseline after EtOH access was terminated (n=3). Effects of DA receptor antagonists on cocaine self-administration were not consistently altered after EtOH consumption, but the ability of quinpirole to induce yawning was enhanced in two of three monkeys. Acute EtOH infusions only decreased self-administration of lower cocaine doses.
  
  
  CONCLUSIONS
  Taken together, the data suggest that long-term EtOH exposure can increase sensitivity to cocaine, possibly by increasing D3 receptor sensitivity. Data do not support a role for acute pharmacological interactions in promoting cocaine/EtOH co-abuse.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157-1083, United States. Electronic address: pczoty@wakehealth.edu.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Czoty
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D019257:Quinpirole / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000378:metabolism; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D015000:Yawning / Q000187:drug effects
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D019257:Quinpirole; D000431:Ethanol; D003042:Cocaine
keywords: Alcohol; Co-abuse; Cocaine; Nonhuman primates; Self-administration