Faculty Collaboration Database

Cannabinoid receptor involvement in stress-induced cocaine reinstatement: potential interaction with noradrenergic pathways. Neuroscience 2012 Mar 01;204:117-24

Date

08/30/2011

Pubmed ID

21871539

Pubmed Central ID

PMC3422566

DOI

10.1016/j.neuroscience.2011.08.021

Scopus ID

2-s2.0-84857125721 (requires institutional sign-in at Scopus site)   37 Citations

Abstract

This study examined the role of endocannabinoid signaling in stress-induced reinstatement of cocaine seeking and explored the interaction between noradrenergic and endocannabinergic systems in the process. A well-validated preclinical model for human relapse, the rodent conditioned place preference assay, was used. Cocaine-induced place preference was established in C57BL/6 mice using injections of 15 mg/kg cocaine. Following extinction of preference for the cocaine-paired environment, reinstatement of place preference was determined following 6 min of swim stress or cocaine injection (15 mg/kg, i.p.). The role of endocannabinoid signaling was studied using the cannabinoid antagonist AM-251 (3 mg/kg, i.p.). Another cohort of mice was tested for reinstatement following administration of the cannabinoid agonist CP 55,940 (10, 20, or 40 μg/kg, i.p.). The alpha-2 adrenergic antagonist BRL-44408 (5 mg/kg, i.p.) with or without CP 55,940 (20 μg/kg) was administered to a third group of mice. We found that: (1) AM-251 blocked forced swim-induced, but not cocaine-induced, reinstatement of cocaine-seeking behavior; (2) the cannabinoid agonist CP 55,940 did not reinstate cocaine-seeking behavior when administered alone but did synergize with a non-reinstating dose of the alpha-2 adrenergic antagonist BRL-44408 to cause reinstatement. These results are consistent with the hypothesis that stress exposure triggers the endogenous activation of CB1 receptors and that activation of the endocannabinoid system is required for the stress-induced relapse of the mice to cocaine seeking. Further, the data suggest that the endocannabinoid system interacts with noradrenergic mechanisms to influence stress-induced reinstatement of cocaine-seeking behavior.

Author List

Vaughn LK, Mantsch JR, Vranjkovic O, Stroh G, Lacourt M, Kreutter M, Hillard CJ

Authors

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
John Mantsch PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenergic alpha-Antagonists
Animals
Behavior, Addictive
Cannabinoids
Cocaine
Cyclohexanols
Dopamine Uptake Inhibitors
Drug-Seeking Behavior
Extinction, Psychological
Imidazoles
Isoindoles
Male
Mice
Piperidines
Pyrazoles
Receptor, Cannabinoid, CB1
Self Administration
Stress, Psychological