Changes in morphine self-administration after brainstem lesions in rats.

Rats were trained to bar press for intravenous infusions of morphine sulfate during 1-h daily test regions. Rates of morphine self-administration were reduced by bilateral lesions of the substantia nigra and enhanced by lesions of the medial raphe nucleus. Dose-response studies indicated that sensitivity to morphine's rewarding property was increased by substantia nigra lesions and decreased by medial raphe lesions. Lesions of the dorsal raphe nucleus and of the locus coeruleus had no effect on self-administration behavior. An interaction between ascending dopaminergic and serotonergic pathways appears to be involved in the mechanism of morphine reinforcement.