ROLE OF PARS COMPACTA OF THE SUBSTANTIA NIGRA IN CIRCLING BEHAVIOR

The significance of pars compacta of the substantia nigra in the mediation of ci circling behavior was assessed by placing unilateral radio-frequency lesions in that neural region, in adjoining tegmental areas, or in the median raphe and adjacent reticular formation; additional ablations were made by infusing 8 μg/4 μl 6-hydroxydopamine (6-OHDA) into the ventral mesencephalon. Rotational behavior was recorded in a photocell apparatus during 15 min sessions. Precise and virtually complete lesions of pars compacta, as evidenced by histological and histochemical analyses, resulted in spontaneous contralateral circling for a postoperative period of 5 days. More vigorous and sustained contralateral rotations were observed in animals with lesions in the region of the median raphe. Other thermal or 6-OHDA mesencephalic lesions did not produce spontaneous circling. On postoperative days 9-23, the animals were administered in random sequence d-amphetamine (1.5 and 5.0 mg/kg) and apomorphine (1.0 mg/kg). At least 48 hr separated each drug test. Amphetamine (1) facilitated contralateral turning in animals with damage to the median raphe and adjacent regions but induced ipsilateral circling in animals sustaining variable degrees of pars compacta damage as a result of midbrain 6-OHDA injections, (2) produced ipsilateral turning in rats with lesions involving portions of pars compacta in addition to the medial lemniscus (at 1.5 but not 5.0 mg/kg drug), pars reticulata (at 5.0 but not 1.5 mg/kg drug), or the ventromedial tegmentum and, in some cases, subthalamic regions (at 5.0 but not 1.5 mg/kg drug), and (3) had no effect upon circling in animals with discrete pars compacta lesions in a dose of 1.5 mg/kg but produced ipsiversive circling after 5.0 mg/kg. Apomorphine did not elicit turning in animals with relatively precise lesions of pars compacta but did produce turning in experimental groups that sustained simultaneous damage to pars compacta and additional systems including portions of the ventromedial tegmentum, pars reticulata of the substantia nigra, or medial lemniscus. The contralateral turning induced by apomorphine in rats with 6-OHDA or radio-frequency lesions of the ventral mesencephalon suggests that mechanisms mediating this drug-induced behavior, although previously attributed almost exclusively to dysfunctions in nigral function, probably include systems involving extra-nigral regions as well. Coupling this consideration with the finding that lesions in the median raphe and contiguous areas elicited more intense circling than nigral ablations suggests that the role of pars compacta in rotational behavior may be less significant than previously believed. © 1979.