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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

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, …

Cb1 Receptor Antagonism Blocks Stress-Potentiated Reinstatement Of Cocaine Seeking In Rats, Jayme R. Mcreynolds, Elizabeth M. Doncheck, Oliver Vranjkovic, Geoffrey S. Ganzman, David A. Baker, Cecilia J. Hillard, John R. Mantsch

Biomedical Sciences Faculty Research and Publications

Rationale

Under some conditions, stress, rather than directly triggering cocaine seeking, potentiates reinstatement to other stimuli, including a subthreshold cocaine dose. The mechanisms responsible for stress-potentiated reinstatement are not well defined. Endocannabinoid signaling is increased by stress and regulates synaptic transmission in brain regions implicated in motivated behavior.

Objectives

The objective of this study was to test the hypothesis that cannabinoid type 1 receptor (CB1R) signaling is required for stress-potentiated reinstatement of cocaine seeking in rats.

Methods

Following i.v. cocaine self-administration (2 h access/day) and extinction in male rats, footshock stress alone does not reinstate cocaine seeking but reinstatement is …

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 …

Drug Predictive Cues Activate Aversion-Sensitive Striatal Neurons That Encode Drug Seeking, Daniel S. Wheeler, Mykel A. Robble, Emily M. Hebron, Matthew J. Dupont, Amanda L. Ebben, Robert A. Wheeler

Biomedical Sciences Faculty Research and Publications

Drug-associated cues have profound effects on an addict’s emotional state and drug-seeking behavior. Although this influence must involve the motivational neural system that initiates and encodes the drug-seeking act, surprisingly little is known about the nature of such physiological events and their motivational consequences. Three experiments investigated the effect of a cocaine-predictive stimulus on dopamine signaling, neuronal activity, and reinstatement of cocaine seeking. In all experiments, rats were divided into two groups (paired and unpaired), and trained to self-administer cocaine in the presence of a tone that signaled the immediate availability of the drug. For rats in the paired group, …

Interactions Among Positions In The Third And Fourth Membrane-Associated Domains At The Intersubunit Interface Of The N-Methyl-D-Aspartate Receptor Forming Sites Of Alcohol Action, Hong Ren, Yulin Zhao, Donard S. Dwyer, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

The N-methyl-d-aspartate (NMDA) glutamate receptor is a major target of ethanol in the brain. Previous studies have identified positions in the third and fourth membrane-associated (M) domains of the NMDA receptor GluN1 and GluN2A subunits that influence alcohol sensitivity. The predicted structure of the NMDA receptor, based on that of the related GluA2 subunit, indicates a close apposition of the alcohol-sensitive positions in M3 and M4 between the two subunit types. We tested the hypothesis that these positions interact to regulate receptor kinetics and ethanol sensitivity by using dual substitution mutants. In single-substitution mutants, we found that a position …

Performance Of A Brief Assessment Tool For Identifying Substance Use Disorders, Todd Campbell, Norman G. Hoffman, Michael B. Madson, Timothy Melchert

College of Education Faculty Research and Publications

Objective: Evaluation of the performance of a brief assessment tool for identifying substance use disorders. The Triage Assessment for Addictive Disorders (TAAD) is a triage instrument that provides professionals with a tool to evaluate indications of current substance use disorders in accordance with the DSM-IV diagnostic criteria. The TAAD is a 31-item structured interview that addresses both alcohol and other drug issues to discriminate among those with no clear indications of a diagnosis, those with definite, current indications of abuse or dependence, and those with inconclusive diagnostic indications.

Methods: Employing a sample of 1325 women between the ages of 18 …