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However, the effects of CB receptor stimulation on nicotine self\u2010administration and reinstatement have not been systematically studied. Here, we studied the effects of WIN 55,212\u20102, a CB1\/2 agonist, on intravenous nicotine self\u2010administration under fixed\u2010ratio (FR) and progressive\u2010ratio (PR) schedules of reinforcement in rats. The effects of WIN 55,212\u20102 on responding for food under similar schedules were also studied. In addition, the effects of WIN 55,212\u20102 on nicotine\u2010 and cue\u2010induced reinstatement of nicotine seeking were also studied, as well as the effects of WIN 55,212\u20102 on nicotine discrimination. WIN 55,212\u20102 decreased nicotine self\u2010administration under the FR schedule. However, co\u2010administration of WIN 55,212\u20102 with nicotine decreased responding for food, which suggests that this effect was non\u2010selective. In contrast, WIN 55,212\u20102 increased both nicotine self\u2010administration and responding for food under the PR schedule, produced dose\u2010dependent reinstatement of nicotine seeking, and enhanced the reinstatement effects of nicotine\u2010associated cues. Some of these effects were reversed by the CB1 antagonist rimonabant, but not by the CB2 antagonist AM630. In the drug discrimination tests between saline and 0.4\u2003mg\/kg nicotine, WIN 55,212\u20102 produced no nicotine\u2010like discriminative effects but significantly potentiated discriminative stimulus effects of nicotine at the low dose through a CB1\u2010receptor\u2010dependent mechanism. These findings indicate that cannabinoid CB1\u2010receptor stimulation increases the reinforcing effects of nicotine and precipitates relapse to nicotine\u2010seeking behaviour in abstinent subjects. Thus, modulating CB1\u2010receptor signalling might have therapeutic value for treating nicotine dependence.<\/jats:p>","DOI":"10.1111\/j.1369-1600.2011.00314.x","type":"journal-article","created":{"date-parts":[[2011,4,26]],"date-time":"2011-04-26T14:09:51Z","timestamp":1303826991000},"page":"47-61","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Cannabinoid receptor stimulation increases motivation for nicotine and nicotine seeking"],"prefix":"10.1111","volume":"17","author":[{"given":"Islam","family":"Gamaleddin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Wertheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy Z.X.","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen 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