EFFECTS OF FULL D-1 DOPAMINE-RECEPTOR AGONISTS ON FIRING RATES IN THEGLOBUS-PALLIDUS AND SUBSTANTIA-NIGRA PARS COMPACTA IN-VIVO - TESTS FOR D-1 RECEPTOR SELECTIVITY AND COMPARISONS TO THE PARTIAL AGONIST SKF-38393

Many studies have used the D-1 agonist SKF 38393 to characterize D-1 r eceptor influences on firing rates in basal ganglia nuclei in vivo. Ho wever, SKF 38393 is a partial agonist and so may not be ideal for deli neating D-1 receptor effects. This study characterizes the effects of four full D-1 agonists, SKF 82958 (chloro-APB), SKF 81297 (6-chloro-PB ), dihydrexidine and A-77636, on the firing rates of midbrain dopamine and globus pallidus neurons. Recordings were done in fully anesthetiz ed or paralyzed, locally anesthetized rats, and drugs were given syste mically intravenously. Dihydrexidine, SKF 81297 and A-77636 were free of rate effects on midbrain dopamine neurons (up to 10.2 mg/kg) and al so did not antagonize the inhibitory effects of quinpirole. In contras t, SKF 82958 strongly inhibited dopamine cells through activation of D -2 autoreceptors (ED50 = 0.70 mg/kg). Of these drugs, SKF 82958 also w as the only one to increase pallidal unit firing rates when given alon e (at 5.0 but not 1.0 mg/kg); the other compounds appeared to be selec tive for postsynaptic D-1 receptors. The results suggest that SKF 8295 8 may be more properly classified as a mixed D-1/D-2 agonist. In addit ion, all four agonists strongly potentiated the pallidal response to q uinpirole, demonstrating a D-1 receptor potentiation of D-2 receptor e ffects. The results support the role of D-1 receptors in the midbrain and globus pallidus as previously characterized with SKF 38393. The si milar actions of partial and full D-1 agonists in these systems suppor t evidence for a D-1 receptor reserve and possibly an effector system other than adenylate cyclase.