Increased entrances to side compartments indicate incubation of craving in morphine-induced rat and tree shrew CPP models

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Abstract

In humans, cues associated with the rewarding effect of drugs of abuse induce drug craving and activate drug-associated memories after prolonged abstinence. In animal studies with the self-administration (SA) paradigm, responses to drug-associated cues increase within time after extinction, a phenomenon described as incubation of craving. Conditioned place preference (CPP) is widely used to measure the rewarding effect of drugs and the reward memory thereof. However, little is known whether responses to drug associated cues progressively increase after abstinence from the drugs in the CPP paradigm. To test whether the drug-associated cues could increase specific responses over the abstinence period in the CPP paradigm, we employed the high dose morphine-induced CPP paradigms in rats and tree shrews in the present study. We examined the CPP scores and the entrances to side chambers of the CPP apparatus to check whether they would progressively increase in the CPP paradigms. Twenty-one male adult Sprague-Dawley rats and eight adult male tree shrews were used to establish morphine-induced CPP and another ten rats treated with saline were controls for the rat experiments. After morphine conditioning, rats and tree shrews showed significant higher CPP scores at the first or second post tests than at baseline but then the CPP scores in the abstinence period decreased gradually. During the abstinence period, animals with morphine-conditioning experiences entered progressively more times to both side compartments, whereas the number of entrances to side chambers of the saline group in rats had no such significant differences. These findings suggest that progressively increased entrances to the side chambers in the extended abstinence period reflect the incubation of craving in high dose morphine-induced CPP paradigms. Also, our data imply that reward memory and drug craving can be distinguished in the CPP paradigm.

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