Circling behavior after narcotic drugs and during naloxone-precipitated abstinence in rats with unilateral nigral lesions

Abstract

Unilateral lesions of the substantia nigra zona compacta (SNC) in rats were produced by electrolytic coagulation or by an injection of 6-hydroxydopamine. Two to 5 weeks later, after being preselected for amphetamine-induced ipsilateral circling behavior, the animals were administered narcotic agonists or antagonists and their circling behavior was observed. Morphine, methadone, levorphanol, nalorphine or pentazocine induced ipsilateral circling movements; both naloxone and dextrorphan were without effect. Ipsilateral circling was also observed in rats with unilateral electrolytic lesions after administration of agents that are thought to enhance central dopaminergic activities: d-amphetamine, l-dopa and apomorphine. In rats with unilateral electrolytic or 6-hydroxydopamine SNC lesions that were rendered highly morphine-dependent by multiple-morphine pellet implantation, contralateral (C) circling behavior was observed within 1 to 2 minutes after a naloxone challenge; the onset and duration of C circling behavior coincided with the initial appearance and duration of precipitated-morphine withdrawal signs. C circling was also observed after administration of putative dopamine receptor blockers, haloperidol and pimozide in rats with either unilateral electrolytic or 6-hydroxydopamine SNC lesions. Morphine pretreatment diminished both the C circling intensity and the appearance of withdrawal signs observed after a naloxone challenge in morphine-dependent, SNC-lesioned rats. The naloxone-precipitated withdrawal in unilaterally lesioned morphine-dependent rats was accompanied by a 20% elevation of neostriatal dopamine in the intact side. In contrast to the effects of a chronic SNC lesion in decreasing neostriatal dopamine, a 77% increase was observed in the lesioned side 30 minutes after electrolytic coagulation. Thus, narcotic agonists and partial agonists may enhance central dopaminergic activities and naloxone-precipitated withdrawal may involve a diminution in central dopaminergic activities of the nigroneostriatal pathway.