Aripiprazole blocks reinstatement of cocaine seeking in an animal model of relapse.
BACKGROUND
Aripiprazole (Abilify) is an atypical antipsychotic drug primarily characterized by partial agonist activity at dopamine (DA) D2 receptors and low side effects. Based on pharmacologic properties that include a stabilization of mesocorticolimbic DA activity, a pathway implicated in addiction, aripiprazole was tested for its ability to prevent relapse to cocaine seeking in rats.


METHODS
We assessed the dose-dependent effects of aripiprazole on conditioned cue-induced and cocaine-primed reinstatement of drug-seeking behavior following chronic intravenous cocaine self-administration in an animal model of relapse.


RESULTS
Aripiprazole potently and dose-dependently attenuated responding on the previously cocaine-paired lever during both reinstatement conditions, with slightly greater efficacy at reducing conditioned-cued reinstatement. Aripiprazole was effective at doses that failed to alter cocaine self-administration, food self-administration, reinstatement of food-seeking behavior, or basal locomotor activity, suggesting selective effects of aripiprazole on motivated drug-seeking behavior.


CONCLUSIONS
These results in a relapse model show that aripiprazole can block cocaine seeking without affecting other behaviors. The D2 partial agonist properties of aripiprazole likely account for the blockade of reinstatement of cocaine-seeking behavior. Given its established efficacy and tolerability as a treatment for psychosis, aripiprazole may be an excellent therapeutic choice for reducing craving and preventing relapse in people with cocaine dependency.
Feltenstein
Matthew W
MW
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Altar
C Anthony
CA
See
Ronald E
RE
D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole; D016739:Behavior, Addictive / Q000209:etiology / Q000517:prevention & control*; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000150:complications / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000627:therapeutic use*; D015363:Quinolones / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055502:Secondary Prevention; D012646:Self Administration / Q000379:methods
D014150:Antipsychotic Agents; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D003042:Cocaine