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

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.