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Neuropsychopharmacology (2007) 32, 22382247 & 2007 Nature Publishing Group All rights reserved 0893-133X/07 $30.00
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Effect of Aripiprazole, a Partial Dopamine D2 Receptor Agonist, on Increased Rate of Methamphetamine Self-Administration in Rats with Prolonged Session Duration
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INTRODUCTION Methamphetamine is an N-methyl amphetamine analog that can be easily synthesized and has high-abuse potential. A recent report by the Community Epidemiology Work Group (2004) indicated a notable increase in methamphetamine treatment admissions in Atlanta and Minneapolis/St Paul, besides San Diego and Hawaii, suggesting an eastward spread of the drug. Similarly, the National Survey on Drug Use and Health noted an increase from 27.5% (2002) to59.3% (2004) in the number of past month methampheta-mine users who met the criteria for dependence. This epidemic of methamphetamine abuse prompted the development of pharmacological interventions of methampheta-mine abuse.
Sunmee Wee*,1, Zhixia Wang2, William L Woolverton2, Luigi Pulvirenti1 and George F Koob1
1Committee on Neurobiology of Addictive Disorder, The Scripps Research Institute, La Jolla, CA, USA; 2Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA
Aripiprazole is a dopamine (DA) D2 receptor partial agonist, approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia. DA receptor partial agonists have been previously assessed as potential therapeutic agents for cocaine dependence. The present experiment examined the effect of aripiprazole on methamphetamine self-administration in a rodent model of an increasing drug self-administration with prolonged session duration. Wistar rats were allowed to self-administer methamphetamine (0.05 mg/kg/injection, intravenously) in either 1-h (short access: ShA rats) or 6-h sessions (long access: LgA rats). After 15 sessions, the doseresponse function of methamphetamine was determined under either a progressive- or a fixed-ratio schedule. Next, the effect of aripiprazole (0.310 mg/ kg, subcutaneuously (s.c.)) on the doseresponse function was examined. LgA rats exhibited an increasing rate of methamphetamine self-administration. Responding for methamphetamine by LgA rats was higher than that of ShA rats under both schedules. Pretreatment with aripiprazole shifted the doseresponse function of methamphetamine to the right in both LgA and ShA rats. However, the effect of aripiprazole was greater in LgA than ShA rats. In in vitro receptor...