SR141716A reduces the reinforcing properties of heroin but not heroin‐induced increases in nucleus accumbens dopamine in rats

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Abstract
The present experiments tested the hypothesis that the selective CB1 receptor antagonist SR141716A alters heroin self‐administration by attenuating heroin‐induced increases in nucleus accumbens dopamine levels. SR141716A pretreatment dose‐dependently (0.3–3 mg/kg, i.p.) reduced operant heroin self‐administration by male Wistar rats under a fixed ratio schedule of reinforcement, and significantly lowered the breaking point of responding for heroin under a progressive ratio schedule of reinforcement. These observations are consistent with recent reports that CB1 receptor inactivation reduces the rewarding properties of opiates. Operant responding for water reinforcement by water‐restricted rats was unaltered by these SR141716A doses. Microdialysis tests revealed that heroin self‐administration significantly increases interstitial dopamine levels in the nucleus accumbens shell of vehicle‐pretreated control rats. However, whereas SR141716A pretreatment dose‐dependently reduced heroin self‐administration, it did not alter the heroin‐associated increase in nucleus accumbens dopamine. These findings suggest that the CB1 antagonist‐induced attenuation of heroin reward does not involve dopaminergic mechanisms in the nucleus accumbens shell.