Development of dopamine receptor denervation supersensitivity in the neostriatum of the senescent rat

Dopamine (DA) stimulated adenylate cyclase activity and [³H]-spiroperidol specific binding were assessed in the striata from mature and old rats lesioned in the left substantia nigra with 6-hydroxydopamine (6-OHDA). Rotational behavior following the DA releasing agent, amphetamine, and the DA receptor agonist, lergotril, was also examined at 7 and 30 days, respectively, after lesioning. Results indicated that while there were rotational behavioral deficits following amphetamine in the senescent animal, none were seen with respect to lergotril. Both old and young animals showed similar degrees of contralateral rotation (with respect to the lesion) following lergotril administration. This suggested that both old and young animals showed similar development of denervation supersensitivity in the DA receptors of the lesioned striatum. Subsequent biochemical confirmation of this hypothesis was provided by findings which showed comparable relative increases in DA stimulated adenylate cyclase activity and [³H]-spiroperidol specific binding in the striata from the lesioned hemispheres of young and old rats. Additionally, high positive correlations were found between rotation and [³H]-spiroperidol specific binding, while those between DA stimulated adenylate cyclase activity and rotation were lower and dependent upon the concentration of DA used to stimulate adenylate cyclase activity (1, 5 and 100 uM). Results are discussed in terms of the specificity of the age-related deficits seen in the striatum of the senescent animal.