CRF-CRF1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats.
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SUBMITTER: George O
PROVIDER: S-EPMC2040467 | biostudies-literature | 2007 Oct
REPOSITORIES: biostudies-literature
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CRF-CRF1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats.
George Olivier O Ghozland Sandy S Azar Marc R MR Cottone Pietro P Zorrilla Eric P EP Parsons Loren H LH O'Dell Laura E LE Richardson Heather N HN Koob George F GF
Proceedings of the National Academy of Sciences of the United States of America 20071005 43
Nicotine, the main psychoactive ingredient of tobacco, induces negative emotional symptoms during abstinence that contribute to a profound craving for nicotine. However, the neurobiological mechanisms underlying how nicotine produces dependence remains poorly understood. We demonstrate one mechanism for both the anxiety-like symptoms of withdrawal and excessive nicotine intake observed after abstinence, through recruitment of the extrahypothalamic stress peptide corticotropin-releasing factor (C ...[more]
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Project description:Most people start experimenting with tobacco products or e-cigarettes in early adolescence and become habitual smokers in late adolescence or adulthood. These studies investigated if exposure to tobacco smoke or nicotine during early and mid-adolescence affects nicotine intake in late adolescence and early adulthood. Male and female rats were exposed to tobacco smoke from low- and high-nicotine SPECTRUM cigarettes or nicotine (0.3 mg/kg, twice a day) from postnatal day (P) 24-42. The self-administration sessions started at P55. The rats self-administered nicotine for 14-15 days under a fixed-ratio 1 schedule, and on the first day, the maximum number of infusions was twenty. Exposure to smoke from high, but not low, nicotine cigarettes during adolescence increased nicotine self-administration in female but not male rats. Adolescent treatment with nicotine facilitated nicotine self-administration. On the first day of nicotine self-administration, nicotine-treated rats reached the maximum number of infusions before the saline-treated control rats. Nicotine intake was also higher in the nicotine-treated female rats than in the saline-treated females. There was no sex difference in nicotine intake in controls when the data from the studies were combined. Smoke exposure led to a dose-dependent increase in plasma nicotine and cotinine levels in adolescent rats. Exposure to smoke from high-nicotine cigarettes and 0.3 mg/kg of nicotine led to plasma nicotine and cotinine levels that are similar to those in tobacco users. These findings indicate that in females, but not males, exposure to nicotine during adolescence may facilitate smoking and e-cigarette use later in life.
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