EFFECTS OF DOPAMINERGIC AGENTS ON REVERSAL OF RESERPINE-INDUCED IMPAIRMENT IN CONDITIONED AVOIDANCE-RESPONSE IN RATS

Male Slc:Wistar, Std:Wistar, and Slc:F344/N rats had good acquisition of the conditioned avoidance response (CAR), while that of the male Sl c:Wistar/ST, Jcl:Wistar, and Crj:Wistar rats was bad. Reserpine-induce d impairment (RII) in CAR was observed 2-72 h after administration of dopaminergic (DAergic) agents in male Slc:Wistar rats. Amitriptyline ( 5-80 mg/kg, PO), imipramine, desipramine, cis-dosulepine, and trans-do sulepine at dose of 40 mg/kg, PO showed no antagonism against RII in C AR 20-23 h after reserpine injection (1 mg/kg, SC). However, the atypi cal antidepressive agents sibutramine (5-10 mg/kg, PO), bupropion (40 mg/kg, PO), and nomifensine (10-40 mg/kg, PO) exhibited antagonism aga inst RII in CAR. The calcium channel antagonists flunarizine, nimodipi ne, and KP-840 at dose of 10 and 100 mg/kg, PO, the cerebral improving agent indeloxazine (20-80 mg/kg, PO), the anticholinergic agent atrop ine (5-40 mg/kg, PO), 5-hydroxy-L-tryptophan (5-HTP) (40 mg/kg, IF), a precursor of 5-hydroxytryptamine (5-HT), and (+/-)-threo-dihydroxyphe nylserine [(+/-)-threo-DOPS] (20-200 mg/kg PO), a norepinephrine (NE) precursor, showed no antagonism against RII in CAR. The DAergic agents methamphetamine (5 mg/kg, PO) and amantadine (50-250 mg/kg, PO), L-DO PA (200 mg/kg, PO), and the DAergic D-1/D-2 receptor agonist apomorphi ne (0.1-1 mg/kg, SC) showed marked antagonism against RII in CAR. Alth ough the DAergic D-1-receptor agonist KF-38393 (0.3-30 mg/kg, IP) and the DAergic D-2-receptor agonist quinpirole (0.3-10 mg/ kg, IF) induce d only a weak recovery of RII in CAR when they were administered alone , in contrast to a potent synergistic recovery of RII in CAR, which wa s observed when SKF-38393 (1 mg/kg, IP) and quinpirole (1 mg/kg, IF) w ere administered together. These results suggest that the DAergic nerv ous system rather than the adrenergic or 5-HT nervous system is involv ed in RII in CAR, and that both the DAergic D-1-and D-2-mediated nervo us systems play important roles in this process. (C) 1997 Elsevier Sci ence Inc.