Effects of Dopaminergic Agents on Reversal of Reserpine-Induced Impairment in Conditioned Avoidance Response in Rats

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 1997-12, Vol.58 (4), p.829-836
• Main Authors: Nakagawa, Terutake, Ukai, Kiyoharu, Ohyama, Tadashi, Gomita, Yutaka, Okamura, Hitoshi
• Format: Article
• Language: English
• Subjects: Animals; Antidepressive agents; Antidepressive Agents, Tricyclic - pharmacology; Antipsychotic Agents - antagonists & inhibitors; Antipsychotic Agents - pharmacology; Avoidance Learning - drug effects; Biological and medical sciences; Calcium channel antagonists; D 1 and D 2 interaction; DAergic agonists; Dopamine Agents - pharmacology; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Learning Disorders - chemically induced; Learning Disorders - psychology; Male; Medical sciences; Monoamine uptake inhibitor; Pharmacology. Drug treatments; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Dopamine D1 - antagonists & inhibitors; Reserpine - antagonists & inhibitors; Reserpine - pharmacology; Shuttle box; Species Specificity; Toxicity: nervous system and muscle
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(97)98984-X

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, IP), 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, IP) 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, IP) 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.