title: The dopamine D1 antagonist reduces ethanol reward for C57BL/6 mice.
abstract: BACKGROUND
  Dopamine D1 antagonist effects on behaviors related to obtaining and consuming ethanol remain unclear. The highly selective D1 antagonist ecopipam (SCH 39166), which has no effect on the serotonin system, was used to evaluate the role of D1 receptors in ethanol reward and its potential for treating alcohol abuse by determining its effect on several measures of ethanol reward in C57BL/6 (B6) mice.
  
  
  METHODS
  Ecopipam (0.025-0.2 mg/kg) effects on instrumental and contingent consummatory responses and on noncontingent consummatory responses for ethanol and water reward were determined in food-restricted male mice trained to lever-respond for 12% ethanol delivered on a fixed ratio-4 reinforcement schedule. The mice were tested for 15-min sessions under preprandial (high-hunger and low-thirst) and postprandial (low-hunger and high-thirst) test conditions.
  
  
  RESULTS
  Ecopipam dose-dependently reduced instrumental and consummatory responses for ethanol and ethanol intake when tested under hunger- or thirst-motivated conditions with free access to water. Under thirst motivation with no access to an alternate fluid source, lever responses for ethanol and water were similar; however, ecopipam reduced responding for ethanol more than responding for water reward. When given concurrent free access to the same fluid delivered for lever pressing, animals made more contacts for ethanol than for water; ecopipam reduced free ethanol but not water contacts.
  
  
  CONCLUSIONS
  Ecopipam attenuated ethanol reward at doses that did not affect water reward, indicating an effect independent of reductions in motor system function or general motivation and arousal. Ecopipam also reduced ethanol reward to the same degree under hunger, thirst, or sated conditions, again indicating that it affected ethanol reward at doses that did not grossly affect general motivational states. These data suggest that ecopipam may reduce ethanol reward with few side effects and that it warrants further investigation as a pharmacological tool for treating alcohol abuse.
authors.affiliation: Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, and Department of Physiology and Neurosciences, Medical University of South Carolina, 67 President St., Charleston, SC 29425, USA.
authors.forename: Kimber L
authors.initials: KL
authors.lastname: Price
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Middaugh
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D012201:Reward
chemical_list: D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D000431:Ethanol