Effects Of Morphine Withdrawal On Locomotor Activity And Contextual Fear Conditioning In Mice

Objective: First, to investigate the validity of open field in studying anxiety induced by morphine withdrawal through test the effect of morphine withdrawal on spontaneous activity in mice. Second, to test the influence of morphine withdrawal on the contextual fear conditioning.Methods: Morphine hydrochloride was administrated(sc) to mice in gradually increasing dose for 7d to establish morphine dependence model. After the last injection, animals were divided into MW1d(Morphine Withdrawal1d), MW7d, MW21d SW1d(Saline Withdrawal1d),SW7d and SW21d group randomly, they were tested the spontaneous activity in the open field box after the period of W1d,W7d and W21d respectively, including the number of crossing and rearing, grooming time, the number of center entries and time spent in center area , and time spent in peripheral area. After the test, mice were trained contextual fear conditioning, and tested contextual fear conditioning 24h later.Results:, In W1d morphine group, compared with the saline group, the number of crossing and rearing and center entries , time spent in center area decreased markedly ( p<0.001, p<0.001, p<0.001, p<0.001) , the time spent in grooming and peripheral area increased strikingly(p<0.05,p<0.01), To the W7d morphine group, the number of crossing and center entries , time spent in center area reduced remarkably(p<0.05,p<0.05,p<0.05),meanwhile, the time spent in peripheral area rised(p<0.05). However, the number of rearing, time spent in grooming were not significant difference between the morphine and the saline group(pï¹¥0.05, pï¹¥0.05). All of the indices in the W21d morphine group were not statistical difference from the saline control group(pï¹¥0.05, pï¹¥0.05, pï¹¥0.05, pï¹¥0.05, pï¹¥0.05, pï¹¥0.05). In addition, A history of morphine injections selectively impaired the contextual fear conditioning in W1d group(p<0.05), while there were not notable influence on the W7d or W21d morphine group(pï¹¥0.05, pï¹¥0.05). Conclusion: Firstly, in early withdrawal period, the main indices of spontaneous activity in the morphine-dependent mice had altered significantly, and the alter recovery gradually along with the withdrawal last. It hinted that open field could be a valid model for studying the animal,s anxiety during the early morphine withdrawal period. Secondly, morphine withdrawal could impair the contextual fear conditioning time-dependent.