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Lorcaserin, a 5\u2010HT<jats:sub>2C<\/jats:sub> receptor agonist has been approved in some countries to treat obesity. Based on preclinical and preliminary clinical evidence, lorcaserin may have potential to treat nicotine dependence. These experiments examined in rats the effects of combining varenicline (0.5 or 1\u00a0mg\/kg) and lorcaserin (0.3, 0.6 and 1\u00a0mg\/kg) on nicotine self\u2010administration, reinstatement of nicotine seeking, responding for food and impulsive action. Both drugs alone reduced nicotine self\u2010administration. Combining varenicline and 0.6 mg\/kg lorcaserin reduced responding to a greater extent than either drug alone. In a relapse model, extinguished nicotine seeking was reinstated by a priming injection of nicotine and nicotine\u2010associated cues. Reinstatement was reduced by varenicline (1\u00a0mg\/kg) and by lorcaserin (0.3\u00a0mg\/kg). Combining lorcaserin (0.3\u00a0mg\/kg) with varenicline (0.5 or 1\u00a0mg\/kg) reduced reinstatement to a greater degree than either drug alone. Both drugs had minimal effects on responding for food, alone or in combination. In the five\u2010choice serial reaction time test, varenicline (0.5 or 1\u00a0mg\/kg) increased impulsivity, measured as increased premature responding. This effect was reduced by lorcaserin (0.3\u00a0mg\/kg). Plasma levels of varenicline or lorcaserin were not altered by co\u2010administration of the other drug. Varenicline and lorcaserin have additive effects on nicotine self\u2010administration, and on nicotine seeking. Lorcaserin prevents impulsivity induced by varenicline. This pattern of effects suggests that co\u2010administration of varenicline and lorcaserin has potential as a treatment for nicotine dependence that may exceed the value of either drug alone.<\/jats:p>","DOI":"10.1111\/adb.12602","type":"journal-article","created":{"date-parts":[[2018,3,2]],"date-time":"2018-03-02T08:54:42Z","timestamp":1519980882000},"page":"376-387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Preclinical evidence for combining the 5\u2010<scp>HT<sub>2C<\/sub><\/scp> receptor agonist lorcaserin and varenicline as a treatment for nicotine dependence"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8906-2280","authenticated-orcid":false,"given":"Paul J.","family":"Fletcher","sequence":"first","affiliation":[{"name":"Section of Biopsychology &amp; Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health  Canada"},{"name":"Department of Psychiatry University of Toronto  Canada"},{"name":"Department of Psychology University of Toronto  Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoxia","family":"Li","sequence":"additional","affiliation":[{"name":"Section of Biopsychology &amp; Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health  Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo B.","family":"Silenieks","sequence":"additional","affiliation":[{"name":"InterVivo Solutions Inc  Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cam","family":"MacMillan","sequence":"additional","affiliation":[{"name":"InterVivo Solutions Inc  Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ines","family":"DeLannoy","sequence":"additional","affiliation":[{"name":"InterVivo Solutions Inc  Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy A.","family":"Higgins","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Toronto  Canada"},{"name":"InterVivo Solutions Inc  Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e4439"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","unstructured":"CahillK Lindson\u2010HawleyN ThomasKH FanshaweTR LancasterT(2016)Nicotine receptor partial agonists for smoking cessation. 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