Nicotine and brain-stimulation reward: interactions with morphine, amphetamine and pimozide.

Using a rate-independent discrete trial method of determining thresholds for rewarding electrical intracranial stimulation in rats, we evaluated the pharmacological interaction of nicotine plus morphine, d-amphetamine, or the D2 receptor antagonist, pimozide. Both morphine and amphetamine shifted the dose-response curve for nicotine down and to the left, indicating increased efficacy and potency, respectively. Pimozide at doses that have no effect on performance and only minimal effect on brain-stimulation reward blocked the effect of nicotine. These data suggest that the same dopaminergic substrate that supports the positive reinforcing effects of other drugs of abuse also supports nicotine reward.