Repeated aripiprazole administration attenuates cocaine seeking in a rat model of relapse.
BACKGROUND
Aripiprazole (Abilify) is an atypical antipsychotic drug characterized by partial agonist activity at dopamine (DA) D(2)/D(3) receptors and a low side-effect profile. While we previously demonstrated that acute aripiprazole blocked the reinstatement of cocaine seeking in an animal model of relapse, clinical treatment of relapse prevention necessitates testing the effects of aripiprazole following prolonged abstinence, as well as after repeated administration during withdrawal from cocaine.


OBJECTIVE
We assessed the effects of repeated aripiprazole treatment on cocaine seeking after abstinence and during conditioned cue-induced and cocaine-primed reinstatement in rats.


METHODS
Rats self-administered intravenous cocaine paired with a light + tone stimulus for 10-14 days, followed by 2 weeks of abstinence. Following post-abstinence relapse testing, lever responding was allowed to extinguish, with subsequent reinstatement testing occurring either in the presence of the conditioned stimulus, or after a cocaine-priming injection (10 mg/kg, intraperitoneal (IP)). Following 3 or 7 days of pretreatment, rats received an injection of aripiprazole (0.25, 0.5, and 1.0 mg/kg, IP) or vehicle prior to post-abstinence relapse and reinstatement testing.


RESULTS
Vehicle-pretreated animals showed robust cocaine seeking during relapse and reinstatement testing, an effect that was significantly attenuated by aripiprazole pretreatment, although no lasting effects were found in the absence of acute injection.


CONCLUSIONS
These findings support the possibility that repeated aripiprazole may be an effective therapeutic agent for the prevention of relapse in abstinent cocaine users. Based on its antipsychotic profile, aripiprazole may be particularly useful for individuals diagnosed with comorbid psychoses, such as schizophrenia or bipolar disorder.
Feltenstein
Matthew W
MW
Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA. feltens@musc.edu
Do
Phong H
PH
See
Ronald E
RE
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000068180:Aripiprazole; D016739:Behavior, Addictive / Q000209:etiology / Q000517:prevention & control*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000150:complications / Q000517:prevention & control / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055502:Secondary Prevention; D012646:Self Administration
D014150:Antipsychotic Agents; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D003042:Cocaine