Effects of acute and chronic aripiprazole treatment on choice between cocaine self-administration and food under a concurrent schedule of reinforcement in rats.
BACKGROUND
Dopamine D2-like partial agonists such as aripiprazole have received some attention as potential pharmacotherapies for the treatment of psychostimulant addiction. However, the preclinical evaluations so far have focused on acute effects of aripiprazole.


OBJECTIVE
We tested the hypothesis that aripiprazole, both as acute and as chronic treatment, would preferentially decrease cocaine self-administration while sparing behavior maintained by a natural reinforcer, resulting in a shift in the allocation of behavior from cocaine-taking towards the alternative reinforcer.


METHODS
Rats were trained to self-administer intravenous cocaine in a concurrent choice procedure, with a palatable food as the competing reinforcer, under a fixed ratio (FR) 1 FR 5 chain schedule. Aripiprazole was then administered as continuous infusion by osmotic minipumps for 5 days, during which performance in the choice procedure was assessed daily.


RESULTS
An intermediate dose of aripiprazole decreased cocaine self-administration and shifted the cocaine choice curve to the right as an acute treatment. However, as a chronic treatment, aripiprazole failed to decrease cocaine self-administration or cocaine choice, despite a dose-dependent decrease in overall response rates and food-maintained behavior.


CONCLUSIONS
Our results confirm and extend earlier findings and indicate that acute administration of aripiprazole can decrease cocaine self-administration. However, based on the present data, chronic treatment with aripiprazole does not show much promise as a potential pharmacotherapy for cocaine addiction. Both acute and chronic treatment data are in agreement with published clinical findings, suggesting that the concurrent choice procedure in rats has predictive validity of efficacy in humans.
Thomsen
Morgane
M
Alcohol and Drug Abuse Research Center, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA. mthomsen@mclean.harvard.edu
Fink-Jensen
Anders
A
Woldbye
David P D
DP
Wörtwein
Gitta
G
Sager
Thomas N
TN
Holm
Rene
R
Pepe
Lauren M
LM
Caine
S Barak
SB
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D001522:Behavior, Animal; D002986:Clinical Trials as Topic; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D054333:Drug Partial Agonism; D005527:Food, Fortified / Q000032:analysis*; D007262:Infusions, Intravenous; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists; D012055:Reinforcement Schedule; D012646:Self Administration
D000779:Anesthetics, Local; D014150:Antipsychotic Agents; D010879:Piperazines; D011506:Proteins; D015363:Quinolones; D017448:Receptors, Dopamine D2; D000068180:Aripiprazole; D003042:Cocaine