Dopaminergic-cholinergic interactions in naloxone-induced circling in morphine-dependent rats with nigral lesions

3-4 weeks after placement of a unilateral, electrolytic lesion of the substantia nigra zona compacta, rats were highly dependent on morphine by the s.c. morphine pellet implantation technique. Following challenge with a supramaximal naloxone dose of 20 mg/kg i.p., both continuous contralateral circling behavior and severe withdrawal signs in morphine-dependent, lesioned rats were elicited. After various drug pretreatments, the contralaeral circling behavior precipitated by naloxone was: (a) reversed to ipsilateral circling by i.p. apomorphine or d-amphetamine, (b) unaltered by i.p. haloperidol or intraneostriatal arecoline administered into the intact neostriatum, and (c) reversed to ipsilateral circling by the administration of atropine into the intact neostriatum. Atropine, apomorphine and amphetamine all interfered with the manifestation of naloxone-precipitated abstinence. These data suggest that a diminution of dopaminergic or an enhancement of cholinergic activities, or both, occur at the level of the neostriatum during naloxone-precipitated withdrawal in morphine-dependent rats.