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Am J Translational Res 2011;3(1):81-89

Review Article
Pharmacologically-induced stress: a cross-species probe for
translational research in drug addiction and relapse

Ronald E. See, R. Parrish Waters

Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA

Received October 15, 2010; Accepted October, 2010; Epub October, Published January 1, 2011

Abstract: Stress plays a major role in the process of drug addiction and various stressors are known to increase
measures of craving in drug dependent human laboratory subjects.  Animal models of stress-induced
reinstatement of drug-seeking have also been developed in order to determine the neuropharmacological and
neurobiological features of stress-induced relapse.  Here, we review experimental approaches that use various
pharmacological agents to induce a stress response and subsequent craving or drug-seeking for drugs of
abuse.  The advantages of such an approach are that the exact same stressor can be used in different species,
pharmacological stress activation works on identifiable pathways, and stress levels can be varied via dose
dependent manipulations.  To date, successful use of such probes in both humans and experimental animals
have been achieved with noradrenergic compounds and corticotrophin-releasing hormone (CRH).  Other
possible approaches, such as neuroactive peptides related to central stress responses (e.g., vasopressin and
substance P) and inverse benzodiazepine agonists show some promise, and we discuss recent experiments
using these compounds.  Future development and application of pharmacological stressors across species will
be useful in assessing stress-induced craving and relapse in both human drug addiction and animal models of
relapse.  Through this translational approach, novel treatment interventions for addiction may be designed and
tested. (AJTR1010002).

Key words: Addiction, corticotrophin-releasing hormone, craving, reinstatement, relapse, stress, yohimbine

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Address all correspondence to:
Ronald E. See, PhD
Department of Neurosciences
Medical University of South Carolina
173 Ashley Avenue, BSB 416B
Charleston SC 29425