ABSTRACT
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 SW21 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.