Association Between Nicotine Withdrawal and Reward Responsiveness in Humans and Rats

作者：Pergadia Michele L^*; Der Avakian Andre; D' Souza Manoranjan S; Madden Pamela A F; Heath Andrew C; Shiffman Saul; Markou Athina; Pizzagalli Diego A

来源：JAMA Psychiatry, 2014, 71(11): 1238-1245.

DOI：10.1001/jamapsychiatry.2014.1016

IMPORTANCE Reward-related disturbances after withdrawal from nicotine are hypothesized to contribute to relapse to tobacco smoking but mechanisms underlying and linking such processes remain largely unknown. %26lt;br%26gt;OBJECTIVE To determine whether withdrawal from nicotine affects reward responsiveness (ie, the propensity to modulate behavior as a function of prior reinforcement experience) across species using translational behavioral assessments in humans and rats. %26lt;br%26gt;DESIGN, SETTING, PARTICIPANTS Experimental studies used analogous reward responsiveness tasks in both humans and rats to examine whether reward responsiveness varied in (1) an ad libitum smoking condition compared with a 24-hour acute nicotine abstinence condition in 31 human smokers with (n = 17) or without (n = 14) a history of depression; (2) rats 24 hours after withdrawal from chronic nicotine (n = 19) or saline (n = 20); and (3) rats following acute nicotine exposure after withdrawal from either chronic nicotine or saline administration. %26lt;br%26gt;MAIN OUTCOMES AND MEASURES Performance on a reward responsiveness task under nicotine and nonnicotine conditions. %26lt;br%26gt;RESULTS In both human smokers and nicotine-treated rats, reward responsiveness was significantly reduced after 24-hour withdrawal from nicotine (P %26lt; .05). In humans, withdrawal-induced deficits in reward responsiveness were greater in those with a history of depression. In rats previously exposed to chronic nicotine, acute nicotine reexposure long after withdrawal potentiated reward responsiveness (P %26lt; .05). %26lt;br%26gt;CONCLUSIONS AND RELEVANCE These findings across species converge in suggesting that organisms have diminished ability to modulate behavior as a function of reward during withdrawal of nicotine. This blunting may contribute to relapse to tobacco smoking, particularly in depression-vulnerable individuals, to reinstate responsiveness to natural rewards and to experience potentiated nicotine-induced reward responsiveness. Moreover, demonstration of behavioral homology across humans and rodents provides a strong translational framework for the investigation and development of clinical treatments targeting reward responsiveness deficits during early withdrawal of nicotine.

• 出版日期2014-11