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Incubation of conditioned reward with peripheral cocaine actions as the conditioned stimulus

Wednesday, October 26, 2011 — Poster Session IV

2:00 p.m. – 4:00 p.m.

Natcher Conference Center




  • B Wang
  • R Wise


We have reported that the peripheral effect of cocaine can come to trigger ventral tegmental glutamate release and reinstate cocaine-seeking behavior in cocaine-experienced rats. Here, we investigated whether the peripheral effects of cocaine can become conditioned reinforcers in their own right. Rats were first trained to self-administer intravenous cocaine (1mg/kg/0.13ml, under an FR-1 schedule) or receive yoked cocaine or saline infusions for two weeks. Twenty-four hours after the last cocaine self-administration or yoked session, we determined the ability of cocaine methiodide (a cocaine analogue that does not cross the blood-brain barrier) to serve as a conditioned, second order, reward in a conditioned place preference (CPP) paradigm. We found weak but reliable conditioned place preferences with cocaine methiodide (13 mg/kg, IP) in rats trained to self-administer cocaine but not in cocaine yoke-trained or saline-yoked rats; equimolar cocaine hydrochloride injections established stronger place preferences in rats with similar training. However, when we gave cocaine methiodide at longer delays after cocaine self-administration, we found stronger preferences, mimicking the known incubation of craving effects of peripheral cocaine-predictive cues. Attenuation of peripheral cocaine actions by anti-cocaine antibodies may thus contribute to the effectiveness of this promising approach to treatment for cocaine addiction.

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