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While this \u201cgateway drug effect\u201d is assumed to be related to psychosocial factors, data from our laboratory suggests that adolescent nicotine use may permanently disrupt reward systems through changes in dopamine receptor function. Behavioral pharmacological methods known to be indirectly (motor activity) and directly (conditioned\u2010place\u2010preference) related to drug reinforcement were used to examine changes in cocaine sensitivity. Testing was performed on adult mice that were exposed to nicotine (0.3, 1.0, and 3.0 mg\/kg, SC, M\u2010F, b.i.d.) or saline during adolescence (postnatal days 25\u201357). Prior to testing, subjects had a 28 day drug\u2010free, time\u2010off period. After acclimation to the testing apparatus, the locomotor effects (30 min, 30 cm traveled) of cocaine (5, 10, and 20 mg\/kg, IP) were measured daily; cocaine tests were preceded and followed by saline control tests. Following the acute dose\u2013response curve, mice received saline followed by 5 days of 20.0 mg\/kg cocaine. Thereafter, mice underwent condition\u2010place\u2010preference testing. A pre\u2010test was performed to determine compartment preference (i.e., no injection, 20 min test). Cocaine (10 mg\/kg, IP) was paired with the subjects non\u2010preferred side and saline with the other. Conditioning sessions were conducted for 8 days with the order of drug\/saline injections counter\u2010balanced across subjects. A drug\u2010free, post\u2010test occurred on the day following the final conditioning session. A dose\u2010dependent relationship between adolescent nicotine exposure and cocaine reward was noted in the adult mice across both test conditions. Subjects exposed to nicotine showed an increased response to cocaine's motor activating effects and a decreased response to cocaine's rewarding effects. A follow\u2010up study was undertaken to evaluate dopamine D1, D2, and D3 receptor function in adult mice exposed to the highest dose of nicotine from the first study. While both interesting and revealing, the results of motor activity tests with dopamine agonist only approached significance. Further research will be required to more fully examine the mechanism of action for the observed changes in cocaine reward. In summary, this is the first study to demonstrate a dose\u2013response relationship between adolescent nicotine exposure and changes in cocaine reward and sensitivity during adulthood.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.ijdevneu.2004.04.002","type":"journal-article","created":{"date-parts":[[2004,7,8]],"date-time":"2004-07-08T03:50:17Z","timestamp":1089258617000},"page":"339-348","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Long\u2010term, low\u2010level adolescent nicotine exposure produces dose\u2010dependent changes in cocaine sensitivity and reward in adult mice"],"prefix":"10.1002","volume":"22","author":[{"given":"Brian M.","family":"Kelley","sequence":"first","affiliation":[{"name":"Department of Psychology Bridgewater College 402 East College Street, P.O. 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