Dopamine agonist-induced locomotor activity in rats treated with 6-hydroxydopamine at differing ages: functional supersensitivity of D-1 dopamine receptors in neonatally lesioned rats.

Locomotor responses caused by dopamine receptor agonists with presumed specificity for D-1 or D-2 receptor subtypes were compared to apomorphine-induced locomotion in neonatally and adult 6-hydroxydopamine (6-OHDA)-treated rats. In adult 6-OHDA-treated rats, apomorphine and the D-2 agonist, LY-171555, produced a marked, dose-related increase in locomotor activity. Increases in locomotion observed in neonatally 6-OHDA-treated rats after apomorphine and LY-171555 administration were less than one-third of those seen in rats treated as adults with 6-OHDA. Neonatally 6-OHDA-treated rats, positive for L-dihydroxyphenylalanine-induced self-biting, exhibited a small increase in locomotion after a single exposure to SKF-38393, a D-1 dopamine agonist. Subsequent administration of SKF-38393 to these rats resulted in an additional elevation of the locomotor response which reached a maximum after four doses. Adult 6-OHDA-treated rats were less sensitive to the locomotor stimulant effects of SKF-38393 than were neonatally 6-OHDA-treated rats. SKF-38393 and LY-171555 produced several behaviors in neonatally 6-OHDA-treated rats that were similar. These results indicate that D-1 dopamine receptors contribute to modulation of central dopaminergic function. Haloperidol and cis-flupentixol antagonized apomorphine-induced locomotion comparably in control and adult 6-OHDA-treated rats. The D-1 dopamine receptor antagonist, SCH-23390, was a less effective blocker of apomorphine-induced locomotion in 6-OHDA-treated rats than in controls. Therefore, the ability of SCH-23390 to attenuate apomorphine in control rats is likely dependent upon intact catecholamine-containing neurons.(ABSTRACT TRUNCATED AT 250 WORDS)