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Role of the kappa-opioid receptor system in stress-induced reinstatement of nicotine seeking in rats.
Behav Brain Res. 2014 May 15; 265:188-97.BB

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.

Authors+Show Affiliations

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.Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, 33 Russell St., Toronto, Ontario M5S 2S1, Canada. Electronic address: douglas.funk@camh.ca.Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, 33 Russell St., Toronto, Ontario M5S 2S1, Canada.Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, 33 Russell St., Toronto, Ontario M5S 2S1, Canada.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24583188

Citation

Grella, Stephanie L., et al. "Role of the Kappa-opioid Receptor System in Stress-induced Reinstatement of Nicotine Seeking in Rats." Behavioural Brain Research, vol. 265, 2014, pp. 188-97.
Grella SL, Funk D, Coen K, et al. Role of the kappa-opioid receptor system in stress-induced reinstatement of nicotine seeking in rats. Behav Brain Res. 2014;265:188-97.
Grella, S. L., Funk, D., Coen, K., Li, Z., & Lê, A. D. (2014). Role of the kappa-opioid receptor system in stress-induced reinstatement of nicotine seeking in rats. Behavioural Brain Research, 265, 188-97. https://doi.org/10.1016/j.bbr.2014.02.029
Grella SL, et al. Role of the Kappa-opioid Receptor System in Stress-induced Reinstatement of Nicotine Seeking in Rats. Behav Brain Res. 2014 May 15;265:188-97. PubMed PMID: 24583188.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of the kappa-opioid receptor system in stress-induced reinstatement of nicotine seeking in rats. AU - Grella,Stephanie L, AU - Funk,Douglas, AU - Coen,Kathy, AU - Li,Zhaoxia, AU - Lê,A D, Y1 - 2014/02/28/ PY - 2013/12/12/received PY - 2014/02/14/revised PY - 2014/02/19/accepted PY - 2014/3/4/entrez PY - 2014/3/4/pubmed PY - 2014/11/14/medline KW - Nicotine KW - Nor-binaltorphimine KW - Reinstatement KW - Stress KW - U50,488 KW - Yohimbine SP - 188 EP - 97 JF - Behavioural brain research JO - Behav Brain Res VL - 265 N2 - 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. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/24583188/Role_of_the_kappa_opioid_receptor_system_in_stress_induced_reinstatement_of_nicotine_seeking_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(14)00104-1 DB - PRIME DP - Unbound Medicine ER -