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 Slc:Wistar/ST, Jcl:Wistar, and Crj:Wistar rats was bad. Reserpine-induced 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-dosulepine at dose of 40 mg/kg, PO showed no antagonism against RII in CAR 20-23 h after reserpine injection (1 mg/kg, SC). However, the atypical antidepressive agents sibutramine (5-10 mg/kg, PO), bupropion (40 mg/kg, PO), and nomifensine (10-40 mg/kg, PO) exhibited antagonism against RII in CAR. The calcium channel antagonists flunarizine, nimodipine, 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 atropine (5-40 mg/kg, PO), 5-hydroxy-L-tryptophan (5-HTP) (40 mg/kg, IF), a precursor of 5-hydroxytryptamine (5-HT), and (+/-)-threo-dihydroxyphenylserine [(+/-)-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-DOPA (200 mg/kg, PO), and the DAergic D-1/D-2 receptor agonist apomorphine (0.1-1 mg/kg, SC) showed marked antagonism against RII in CAR. Although 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) induced 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 was observed when SKF-38393 (1 mg/kg, IP) and quinpirole (1 mg/kg, IF) were administered together. These results suggest that the DAergic nervous system rather than the adrenergic or 5-HT nervous system is involved in RII in CAR, and that both the DAergic D-1-and D-2-mediated nervous systems play important roles in this process. (C) 1997 Elsevier Science Inc.