Stress modulation of drug self-administration: implications for addiction comorbidity with post-traumatic stress disorder

Abstract

Drug abuse and dependence present significant health burdens for our society, affecting roughly 10% of the population. Stress likely contributes to the development and persistence of drug use; for example, rates of substance dependence are elevated among individuals diagnosed with post-traumatic stress disorder (PTSD). Thus, understanding the interaction between stress and drug use, and associated neuroadaptations, is key for developing therapies to combat substance use disorders. For this purpose, many rodent models of the effects of stress exposure on substance use have been developed; the models can be classified according to three categories of stress exposure: developmental, adult nonsocial, and adult social. The present review addresses preclinical findings on the effect of each type of trauma on responses to and self-administration of drugs of abuse by focusing on a key exemplar for each category. In addition, the potential efficacy of targeting neuropeptide systems that have been implicated in stress responses and stress system neuroadaptation in order to treat comorbid PTSD and substance abuse will be discussed. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

Figure 1

Temporal modulation of stress effects on drug-seeking in rodents. Stress exposure acutely elevates behavioral responses to drugs of abuse and drug-seeking at all phases of drug self-administration. Post-stress increases in drug-seeking are usually short-lived, dissipating within 24h after cessation of the stressor. The effects of traumatic stress history on drug-seeking begin to emerge again after an interval, postulated to be on the order of days to several weeks depending on the nature and severity of the stressor. These distal stress history-dependent elevations in drug-seeking behavior may persist for weeks or even months, akin to the effects of post-traumatic stress on human drug-seeking.