The acquisition and maintenance of voluntary ethanol drinking in the rat: effects of dopaminergic lesions and naloxone.
Wistar male rats were microinfused bilaterally with 6-hydroxydopamine or vehicle into the ventral tegmental area. After recovery, ethanol drinking was established using a sucrose-fading paradigm, i.e. rats were given twice a day access to drinks containing increasing amounts of ethanol and decreasing amounts of sucrose. Mean daily intakes at each ethanol/sucrose concentration were similar irrespective of the level of dopamine depletion that, in some animals, reached 80-90%. The percentage of rats testing as ethanol preferers in a two-bottle choice test also appeared similar in both the lesioned and control groups. After completing the sucrose-fading protocol, all rats were switched to one access per day during which they were presented with a drink containing 10% ethanol with 5% sucrose. Naloxone administration (15 min before the daily access period) decreased ethanol beverage consumption by about 50%, irrespective of the level of dopamine depletion. Total daily water intake was not altered by naloxone. In a two-bottle choice situation, naloxone suppressed intake of an ethanol drink (10% ethanol/5% sucrose), but not the intake of 5% sucrose alone. Thus, a lesion of the dopaminergic cell bodies that results in extensive depletion of dopamine in mesolimbic target regions produced no measurable effect on intake of the sweetened ethanol drinks during the acquisition phase of the sucrose-fading paradigm. Furthermore, during the maintenance phase of drinking, the marked effect of naloxone in inhibiting ethanol beverage ingestion (but not water ingestion or sucrose alone solutions) occurred despite extensive loss of dopaminergic innervation to telencephalic target regions. A preliminary account of these experiments appeared in an abstract form and as an Internet publication. (Supported by NIAAA grants P50-03510 and T32-0720).
Shoemaker
William J
WJ
Department of Psychiatry, School of Medicine, University of Connecticut Health Center, Farmington Avenue, , Farmington, CT 06030, USA. shoemake@psychiatry.uchc.edu
Vavrousek-Jakuba
Eva
E
Arons
Cynthia D
CD
Kwok
Fung Cho
FC
D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D001931:Brain Mapping; D004298:Dopamine / Q000502:physiology*; D008032:Limbic System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000503:physiopathology; D009042:Motivation; D009270:Naloxone / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013649:Taste / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000503:physiopathology*
D009270:Naloxone; D004298:Dopamine