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JAMA Psychiatry. 2014 Nov;71(11):1238-1245. doi: 10.1001/jamapsychiatry.2014.1016.

Association between nicotine withdrawal and reward responsiveness in humans and rats.

Author information

1
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO.
2
Department of Psychiatry, University of California San Diego.
3
Department of Psychology, University of Pittsburgh.
4
Department of Psychiatry, Harvard Medical School.
#
Contributed equally

Abstract

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.

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.

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.

MAIN OUTCOMES AND MEASURES:

Performance on a reward responsiveness task under nicotine and nonnicotine conditions.

RESULTS:

In both human smokers and nicotine-treated rats, reward responsiveness was significantly reduced after 24-hour withdrawal from nicotine (P < .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 < .05).

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.

PMID:
25208057
PMCID:
PMC4353576
DOI:
10.1001/jamapsychiatry.2014.1016
[Indexed for MEDLINE]
Free PMC Article

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