Furusawa K, Kuribara H, Tadokoro S
Behavior Research Institute, Gunma University School of Medicine, Maebashi, Japan.
Yakubutsu Seishin Kodo. 1987 Jun;7(2):313-20.
Effects of psychotropic drugs on lever-press and shuttle discrete avoidance responses were investigated by the cumulative-dosing procedure in mice. For cumulative determination, doses of drugs were given 3 times every 1 h within the same session. As a control, the intermittent-dosing procedure in which a single dose was given twice a week was also tested. Cumulative-dosing of chlorpromazine, haloperidol, tetrabenazine, diazepam, and pentobarbital all produced dose-dependent suppression in lever-press and shuttle avoidance responses. Each cumulative dose-effect curve for chlorpromazine and haloperidol in both avoidance responses, and for tetrabenazine and diazepam in lever-press avoidance response was almost identical with that obtained by the intermittent dosing. The cumulative effects of tetrabenazine in shuttle avoidance response and pentobarbital in both avoidance responses were weak. In contrast, diazepam suppressed shuttle avoidance response in the cumulative dosing, but not in the intermittent dosing. Cumulative dosing of methamphetamine and morphine increased response rates without marked changes in avoidance rates in the shuttle avoidance response. Cumulative dosing of methamphetamine was less effective than the intermittent dosing. In contrast, the cumulative dose-effect curve for morphine was almost identical with that obtained by the intermittent dosing. The present results indicate that the cumulative-dosing procedure may be applicable to the drug evaluation in lever-press and shuttle avoidance responses.
采用累积给药法在小鼠中研究了精神药物对杠杆按压和穿梭离散回避反应的影响。为进行累积测定，在同一实验环节中，每隔1小时给予3次药物剂量。作为对照，还测试了每周给药两次单剂量的间歇给药法。氯丙嗪、氟哌啶醇、丁苯那嗪、地西泮和戊巴比妥的累积给药均对杠杆按压和穿梭回避反应产生剂量依赖性抑制。氯丙嗪和氟哌啶醇在两种回避反应中的每条累积剂量效应曲线，以及丁苯那嗪和地西泮在杠杆按压回避反应中的累积剂量效应曲线，与间歇给药所得曲线几乎相同。丁苯那嗪在穿梭回避反应中的累积效应以及戊巴比妥在两种回避反应中的累积效应较弱。相反，地西泮在累积给药时抑制穿梭回避反应，但在间歇给药时不抑制。甲基苯丙胺和吗啡的累积给药增加了穿梭回避反应中的反应率，而回避率无明显变化。甲基苯丙胺的累积给药效果不如间歇给药。相反，吗啡的累积剂量效应曲线与间歇给药所得曲线几乎相同。目前的结果表明，累积给药法可能适用于杠杆按压和穿梭回避反应中的药物评价。
