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.
|Original language||English (US)|
|Number of pages||14|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Dec 1 1976|