Nakagawa T, Ukai K, Ohyama T, Gomita Y, Okamura H
Central Research Institute, Kaken Pharmaceutical Co. Ltd., Kyoto, Japan.
Pharmacol Biochem Behav. 1997 Dec;58(4):829-36. 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, 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.
雄性Slc:Wistar、Std:Wistar和Slc:F344/N大鼠对条件性回避反应（CAR）有良好的习得能力，而雄性Slc:Wistar/ST、Jcl:Wistar和Crj:Wistar大鼠的习得能力较差。在雄性Slc:Wistar大鼠中，给予多巴胺能（DAergic）药物后2至72小时观察到利血平诱导的CAR损伤（RII）。阿米替林（5 - 80毫克/千克，口服）、丙咪嗪、地昔帕明、顺式多塞平及反式多塞平（40毫克/千克，口服）在利血平注射（1毫克/千克，皮下注射）后20至23小时对CAR中的RII无拮抗作用。然而，非典型抗抑郁药西布曲明（5 - 10毫克/千克，口服）、安非他酮（40毫克/千克，口服）和诺米芬辛（10 - 40毫克/千克，口服）对CAR中的RII具有拮抗作用。钙通道拮抗剂氟桂利嗪、尼莫地平和KP - 840（10和100毫克/千克，口服）、脑功能改善剂茚达立嗪（20 - 80毫克/千克，口服）、抗胆碱能药物阿托品（5 - 40毫克/千克，口服）、5 - 羟色氨酸（5 - HTP）（40毫克/千克，腹腔注射，5 - 羟色胺（5 - HT）的前体）以及去甲肾上腺素（NE）前体（±） - 苏 - 二羟基苯丝氨酸[（±） - 苏 - DOPS]（20 - 200毫克/千克，口服）对CAR中的RII无拮抗作用。多巴胺能药物甲基苯丙胺（5毫克/千克，口服）、金刚烷胺（50 - 250毫克/千克，口服）、左旋多巴（200毫克/千克，口服）以及多巴胺能D1/D2受体激动剂阿扑吗啡（0.1 - 1毫克/千克，皮下注射）对CAR中的RII具有显著拮抗作用。尽管多巴胺能D1受体激动剂KF - 38393（0.3 - 30毫克/千克，腹腔注射）和多巴胺能D2受体激动剂喹吡罗（0.3 - 10毫克/千克，腹腔注射）单独给药时仅能使CAR中的RII有微弱恢复，但与之形成对比的是，当SKF - 38393（1毫克/千克，腹腔注射）和喹吡罗（1毫克/千克，腹腔注射）联合给药时，观察到CAR中的RII有显著的协同恢复。这些结果表明，在CAR的RII中涉及的是多巴胺能神经系统而非肾上腺素能或5 - HT神经系统，并且多巴胺能D1和D2介导的神经系统在此过程中均起重要作用。
