Stress Promotes Drug Seeking Through Glucocorticoid-Dependent Endocannabinoid Mobilization in the Prelimbic Cortex

Authors

Jayme R. McReynolds, Marquette UniversityFollow
Elizabeth M. Doncheck, Marquette University
Yan Li, Medical College of Wisconsin
Oliver Vranjkovic, Marquette UniversityFollow
Evan N. Graf, Marquette UniversityFollow
Daisuke Ogasawara, The Scripps Research Institute
Benjamin F. Cravatt, The Scripps Research Institute
David A. Baker, Marquette UniversityFollow
Qing-Song Liu, Medical College of WisconsinFollow
Cecilia J. Hillard, Medical College of WisconsinFollow
John R. Mantsch, Marquette UniversityFollow

Document Type

Article

Language

Eng

Publication Date

7-15-2018

Publisher

Elsevier

Source Publication

Biological Psychiatry

Source ISSN

0006-3223

Abstract

Background

Clinical reports suggest that rather than directly driving cocaine use, stress may create a biological context within which other triggers for drug use become more potent. We hypothesize that stress-induced increases in corticosterone “set the stage” for relapse by promoting endocannabinoid-induced attenuation of inhibitory transmission in the prelimbic cortex (PL).

Methods

We have established a rat model for these stage-setting effects of stress. In this model, neither a stressor (electric footshock) nor stress-level corticosterone treatment alone reinstates cocaine seeking following self-administration and extinction, but each treatment potentiates reinstatement in response to an otherwise subthreshold cocaine priming dose (2.5 mg/kg, intraperitoneal). The contributions of endocannabinoid signaling in the PL to the effects of stress-level corticosterone on PL neurotransmission and cocaine seeking were determined using intra-PL microinfusions. Endocannabinoid-dependent effects of corticosterone on inhibitory synaptic transmission in the rat PL were determined using whole-cell recordings in layer V pyramidal neurons.

Results

Corticosterone application attenuated inhibitory synaptic transmission in the PL via cannabinoid receptor type 1 (CB₁R)– and 2-arachidonoylglycerol–dependent inhibition of gamma-aminobutyric acid release without altering postsynaptic responses. The ability of systemic stress-level corticosterone treatment to potentiate cocaine-primed reinstatement was recapitulated by intra-PL injection of corticosterone, the CB₁R agonist WIN 55,212-2, or the monoacylglycerol lipase inhibitor URB602. Corticosterone effects on reinstatement were attenuated by intra-PL injections of either the CB₁R antagonist, AM251, or the diacylglycerol lipase inhibitor, DO34.

Conclusions

These findings suggest that stress-induced increases in corticosterone promote cocaine seeking by mobilizing 2-arachidonoylglycerol in the PL, resulting in CB₁R-mediated attenuation of inhibitory transmission in this brain region.

Comments

Accepted version. Biological Psychiatry Vol. 84, No. 2 (July 15, 2018): 85-94. DOI. © 2017 Society of Biological Psychiatry. Used with permission.

Recommended Citation

McReynolds, Jayme R.; Doncheck, Elizabeth M.; Li, Yan; Vranjkovic, Oliver; Graf, Evan N.; Ogasawara, Daisuke; Cravatt, Benjamin F.; Baker, David A.; Liu, Qing-Song; Hillard, Cecilia J.; and Mantsch, John R., "Stress Promotes Drug Seeking Through Glucocorticoid-Dependent Endocannabinoid Mobilization in the Prelimbic Cortex" (2018). Biological Sciences Faculty Research and Publications. 610.
https://epublications.marquette.edu/bio_fac/610