The Journal of Neuroscience, January 1, 2001, 21(1):340-348
Motivational Effects of Ethanol in DARPP-32 Knock-Out
Mice
Fred O.
Risinger1,
Pierre A.
Freeman1,
Paul
Greengard2, and
Allen A.
Fienberg2, 3
1 Department of Behavioral Neuroscience, Oregon Health
Sciences University, Portland, Oregon 97201-3098, 2 Laboratory of Molecular and Cellular Neuroscience, The
Rockefeller University, New York, New York 10021, and
3 Genomics Institute of the Novartis Research Foundation,
San Diego, California 92121
DARPP-32 (dopamine and adenosine
3',5'-monophosphate-regulated phosphoprotein, 32 kDa) is an important
component of dopaminergic function in brain areas thought to be
important for drug and alcohol addiction. The present experiments
characterized the acquisition of ethanol-induced conditioned taste
aversion, ethanol-induced conditioned place preference, and ethanol
self-administration in DARPP-32 knock-out (KO) mice compared to
wild-type (WT) controls. For taste conditioning, KO and WT mice
received access to 0.2 M NaCl solution followed immediately
by intraperitoneal injection of 0-4 gm/kg ethanol. Ethanol produced
dose-dependent conditioned taste aversion that was the same in both
genotypes. For place conditioning, KO and WT mice received eight
pairings of a tactile stimulus with ethanol (2 gm/kg, i.p.), and a
different stimulus with saline. Ethanol produced increases in locomotor
activity during conditioning, with KO mice showing higher activity
levels after ethanol compared to WT mice. WT mice, but not KO mice,
acquired conditioned preference for the ethanol-paired stimulus.
In the self-administration procedure, KO and WT mice were trained to lever press for access to 10% v/v ethanol. Subsequently, the mice had
23 hr/d access to food, ethanol, and water. Response patterns were
determined using 0-30% v/v ethanol concentrations. WT mice displayed
concentration-dependent responding for ethanol. Responding on the
ethanol lever by KO mice did not change as a function of ethanol
concentration. Saccharin (0.2% w/v) was subsequently added to the
ethanol mixture, and responding was examined at 0, 5, 10, and 20%
ethanol concentrations. Ethanol responding increased in both genotypes,
although WT mice showed higher rates at all concentrations.
Key words:
ethanol; conditioned taste aversion; conditioned place preference; self-administration; reward; reinforcement; DARPP-32 knock-out mice
Copyright © 2001 Society for Neuroscience 0270-6474/01/211340-09$05.00/0
Previous Article | Next Article
