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Behav Brain Res. 2014 May 15;265:188-97. doi: 10.1016/j.bbr.2014.02.029. Epub 2014 Feb 28.

Role of the kappa-opioid receptor system in stress-induced reinstatement of nicotine seeking in rats.

Author information

1
Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, 33 Russell St., Toronto, Ontario M5S 2S1, Canada; Department of Pharmacology & Toxicology, University of Toronto, Medical Sciences Building, Rm 4207, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
2
Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, 33 Russell St., Toronto, Ontario M5S 2S1, Canada. Electronic address: douglas.funk@camh.ca.
3
Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, 33 Russell St., Toronto, Ontario M5S 2S1, Canada.
4
Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, 33 Russell St., Toronto, Ontario M5S 2S1, Canada; Department of Pharmacology & Toxicology, University of Toronto, Medical Sciences Building, Rm 4207, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, 8th Floor, Toronto, Ontario M5T 1R8, Canada.

Abstract

RATIONALE:

The correlation between stress and smoking is well established. The mechanisms that underlie this relationship are, however, unclear. Recent data suggest that the kappa-opioid system is involved in the mediation of negative affective states associated with stress thereby promoting drug addiction and relapse. Pharmacological treatments targeting the kappa-opioid system and this mechanism may prove to be useful therapeutics for nicotine addiction in the future.

OBJECTIVES:

We sought to determine whether there was a stress-specific role of the kappa-opioid system in nicotine seeking behavior.

METHOD:

Groups of male Long Evans rats were trained to self-administer nicotine intravenously; their operant responding for nicotine was extinguished prior to tests of reinstatement. Pretreatment with systemic injections of the kappa-opioid receptor (KOR) antagonist nor-binaltorphimine (nor-BNI) was given prior to tests of stress (systemic injections of yohimbine (YOH)) or cue-induced reinstatement of nicotine seeking. Systemic injections of the KOR agonist U50,488 were also given in a test for reinstatement of nicotine seeking.

RESULTS:

Nor-BNI pretreatment at 1h and 24h prior to testing was able to block YOH-induced, but not cue-induced reinstatement of nicotine seeking. U50,488 reinstated nicotine seeking behavior in a dose-dependent manner.

CONCLUSIONS:

These findings support the hypothesis that the kappa-opioid system is involved in relapse to nicotine seeking induced by stress, but not by conditioned cues. KOR antagonists such as nor-BNI may therefore be useful novel therapeutic agents for decreasing the risk of stress-induced drug relapse.

KEYWORDS:

Nicotine; Nor-binaltorphimine; Reinstatement; Stress; U50,488; Yohimbine

PMID:
24583188
PMCID:
PMC4082245
DOI:
10.1016/j.bbr.2014.02.029
[Indexed for MEDLINE]
Free PMC Article

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