戒断对吗啡依赖小鼠自发活动及场景性恐惧条件化表达的影响

目的:研究不同戒断期对吗啡依赖小鼠自发活动及场景性恐惧条件化表达的影响.方法:以剂量递增法连续皮下注射(sc)盐酸吗啡7 d建立吗啡依赖小鼠模型,随机分成吗啡戒断1 d、吗啡戒断7 d、吗啡戒断21 d组,并设立生理盐水戒断1、7、21 d组作为对照,每组12～13只.戒断后采用旷场实验观察小鼠自发活动(检测穿梭格数、直立次数、理毛时间、中央区活动时间、进入中央次数及外周时间等指标);随后对小鼠进行场景性恐惧条件化,并于24 h后进行恐惧反应(僵直)的检测.结果:与生理盐水对照组相比,吗啡戒断1 d、7 d组小鼠的水平活动度(P＜0.001,P＜0.001)和进入中央区次数(P＜0.001,P＜0.05)明显降低;戒断1 d组小鼠垂直运动也显著下降(P＜0.001);吗啡戒断1 d组的理毛行为增加(P＜0.05);但各吗啡戒断组的中央区、外周活动时间无显著差异.吗啡处理还选择性损害了戒断1 d组小鼠的场景性恐惧条件化表达(P＜0.05).结论:戒断早期降低了吗啡依赖小鼠部分自发活动,同时损害了场景性恐惧条件化表达.

Effects of abstinence on locomotor activity and contextual fear conditioning in morphine-dependent mice?

Objective: To study the impact of different abstinence periods on locomotor activity and contextual fear conditioning in morphine-dependent mice. Methods: Morphine hydrochloride was administrated (sc) to mice at a gradually increasing dose for 7 d to establish morphine-dependent model. After the last injection, animals were divided into MW1 d (Morphine Withdrawal for 1 d), MW7 d, MW21 d, SW1 d(Saline Withdrawal for 1 d) ,SW7 d and SW 21 d groups randomly; the spontaneous activities of mice, including the numbers of crossing and rearing, grooming times, the number of center entries and time spent in center area, and the time spent in peripheral area, were observed in the open field box after different periods of abstinence. After the observation, the mice were trained using eight unconditioned stimulus (0. 5 s; 0. 5 mA foot shock) and contextual fear conditioning was tested 24 h later. Results: The times of crossing and center entries decreased in MW1 d and MW7 d mice (W1 d: P<0. 001, P<0. 001;W7 d: P<0. 001,P<0. 05); the time of rearing in MW1 d group was also decreased significantly (P<0. 001); mice in MW1 d group had more grooming behaviors (P<0. 05). The periods spent in the center and peripheral areas were not significantly different between all the 3 morphine-dependent groups and their corresponding saline withdrawal groups. In addition, a history of morphine injection selectively impaired the contextual fear conditioning in mice of MW1 d group (P<0. 05). Conclusion: During the early period of morphine abstinence, mice have a decreased spontaneous activity and an impaired contextual fear conditioning.