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, P.O.), imipramine, desipramine, cis-dosulepine, and trans-dosulepine at dose of 40 mg/kg, P.O. showed no antagonism against RII in CAR 20-23 h after reserpine injection (1 mg/kg, S.C.). However, the atypical antidepressive agents sibutramine (5-10 mg/kg, P.O.), bupropion (40 mg/kg, P.O.), and nomifensine (10-40 mg/kg, P.O.) exhibited antagonism against RII in CAR. The calcium channel antagonists flunarizine, nimodipine, and KP-840 at dose of 10 and 100 mg/kg, P.O., the cerebral improving agent indeloxazine (20-80 mg/kg, P.O.), the anticholinergic agent atropine (5-40 mg/kg, P.O.), 5-hydroxy-L-tryptophan (5-HTP) (40 mg/kg, I.P.), a precursor of 5-hydroxytryptamine (5-HT), and (+/-)-threo-dihydroxyphenylserine [(+/-)-threo-DOPS] (20-200 mg/kg P.O.), a norepinephrine (NE) precursor, showed no antagonism against RII in CAR. The DAergic agents methamphetamine (5 mg/kg, P.O.) and amantadine (50-250 mg/kg, P.O.), L-DOPA (200 mg/kg, P.O.), and the DAergic D1/D2 receptor agonist apomorphine (0.1-1 mg/kg, S.C.) showed marked antagonism against RII in CAR. Although the DAergic D1-receptor agonist KF-38393 (0.3-30 mg/kg, I.P.) and the DAergic D2-receptor agonist quinpirole (0.3-10 mg/kg, I.P.) 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, I.P.) and quinpirole (1 mg/kg, I.P.) 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 D1- and D2-mediated nervous systems play important roles in this process.
Nakagawa
T
T
Central Research Institute, Kaken Pharmaceutical Co. Ltd., Kyoto, Japan. HQK03171@niftyserve.or.jp
Ukai
K
K
Ohyama
T
T
Gomita
Y
Y
Okamura
H
H
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D007859:Learning Disabilities / Q000139:chemically induced / Q000523:psychology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D012110:Reserpine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013045:Species Specificity
D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D015259:Dopamine Agents; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D012110:Reserpine