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Accumulating evidence suggests that the dorsal hippocampus (DH) plays an important role in mediating drug\u2010seeking and drug\u2010taking behavior and relapse. However, the molecular mechanisms underlying these effects of the DH are unclear. In the present study, we employed a label\u2010free quantitative proteomic approach to analyze the proteins altered in the DH of heroin self\u2010administering rats. A total of 4015 proteins were quantified with high confidence, and 361 proteins showed significant differences compared with the saline control group. Among them, cyclin\u2010dependent kinase 5 (CDK5) and ras homolog family member B (RhoB) were up\u2010regulated in rats with a history of extended access to heroin. Functionally, inhibition of CDK5 in the DH enhanced heroin self\u2010administration, indicating that CDK5 signaling in the DH acts as a homeostatic compensatory mechanism to limit heroin\u2010taking behavior, whereas blockade of the Rho\u2010Rho kinase (ROCK) pathway attenuated context\u2010induced heroin relapse, indicating that RhoB signaling in the DH is required for the retrieval (recall) of addiction memory. Our findings suggest that manipulation of CDK5 signaling in the DH may be essential in determining vulnerability to opiate taking, whereas manipulation of RhoB signaling in the DH may be essential in determining vulnerability to relapse. Overall, the present study suggests that the DH can exert dissociative effects on heroin addiction through CDK5 and RhoB signaling.<\/jats:p>","DOI":"10.1111\/adb.12435","type":"journal-article","created":{"date-parts":[[2016,8,23]],"date-time":"2016-08-23T00:36:46Z","timestamp":1471912606000},"page":"1731-1742","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Dissociative role for dorsal hippocampus in mediating heroin self\u2010administration and relapse through CDK5 and RhoB signaling revealed by proteomic analysis"],"prefix":"10.1111","volume":"22","author":[{"given":"Zhong\u2010Guo","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica and Collaborative Innovation Center for Brain Science Chinese Academy of Sciences  Shanghai 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