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Addiction

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Stress Promotes Drug Seeking Through Glucocorticoid-Dependent Endocannabinoid Mobilization In The Prelimbic Cortex, Jayme R. Mcreynolds, Elizabeth M. Doncheck, Yan Li, Oliver Vranjkovic, Evan N. Graf, Daisuke Ogasawara, Benjamin F. Cravatt, David A. Baker, Qing-Song Liu, Cecilia J. Hillard, John R. Mantsch Jul 2018

Stress Promotes Drug Seeking Through Glucocorticoid-Dependent Endocannabinoid Mobilization In The Prelimbic Cortex, Jayme R. Mcreynolds, Elizabeth M. Doncheck, Yan Li, Oliver Vranjkovic, Evan N. Graf, Daisuke Ogasawara, Benjamin F. Cravatt, David A. Baker, Qing-Song Liu, Cecilia J. Hillard, John R. Mantsch

Biological Sciences Faculty Research and Publications

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, …


Aversive Stimuli Drive Drug Seeking In A State Of Low Dopamine Tone, Robert C. Twining, Daniel S. Wheeler, Amanda L. Ebben, Andre J. Jacobsen, Mykel A. Robble, John R. Mantsch, Robert A. Wheeler May 2015

Aversive Stimuli Drive Drug Seeking In A State Of Low Dopamine Tone, Robert C. Twining, Daniel S. Wheeler, Amanda L. Ebben, Andre J. Jacobsen, Mykel A. Robble, John R. Mantsch, Robert A. Wheeler

Biological Sciences Faculty Research and Publications

Background

Stressors negatively impact emotional state and drive drug seeking, in part, by modulating the activity of the mesolimbic dopamine system. Unfortunately, the rapid regulation of dopamine signaling by the aversive stimuli that cause drug seeking is not well characterized. In a series of experiments, we scrutinized the subsecond regulation of dopamine signaling by the aversive stimulus, quinine, and tested its ability to cause cocaine seeking. Additionally, we examined the midbrain regulation of both dopamine signaling and cocaine seeking by the stress-sensitive peptide, corticotropin releasing factor (CRF).

Methods

Combining fast-scan cyclic voltammetry with behavioral pharmacology, we examined the effect of …