Clinicians and researchers alike have long believed that stressors play a pivotal etiologic role in risk, maintenance, and/or relapse of alcohol and other substance use disorders (SUDs). Numerous seminal and contemporary theories on SUD etiology posit that stressors may motivate drug use and that individuals who use drugs chronically may display altered responses to stressors. We use foundational basic stress biology research as a lens through which to evaluate critically the available evidence to support these key stress–SUD theses in humans. Additionally, we examine the field's success to date in targeting stressors and stress allostasis in treatments for SUDs. We conclude with our recommendations for how best to advance our understanding of the relationship between stressors and drug use, and we discuss clinical implications for treatment development.

These data indicate that resistance exercise decreases the positive reinforcing effects of heroin and produces changes in opioid and dopamine systems in the NAc of heroin-exposed rats.

Background Studies conducted in male rats report that social contact can either facilitate or inhibit drug intake depending on the behavior of social partners. The purpose of the present study was to: (1) examine the effects of social contact on cocaine intake in female rats, (2) examine the behavioral mechanisms by which social contact influences cocaine intake, and (3) examine whether the estrous cycle moderates the effects of social contact on cocaine intake. Methods Female rats were assigned to either isolated or pair-housed conditions in which a social partner either had access to cocaine (cocaine partner) or did not have access to cocaine (abstinent partner). Pair-housed rats were tested in custom-built operant conditioning chambers that allowed both rats to be tested simultaneously in the same chamber. Results Rats housed with a cocaine partner self-administered more cocaine than isolated rats and rats housed with an abstinent partner. A behavioral economic analysis indicated that these differences were driven by a greater intensity of cocaine demand (i.e., greater intake at lower unit prices) in rats housed with a cocaine partner. Multivariate modeling revealed that the estrous cycle did not moderate the effects of social contact on cocaine intake. Conclusions These findings indicate that: (1) social contact influences cocaine self-administration in females in a manner similar to that reported in males, (2) these effects are due to differences in the effects of social contact on the intensity of cocaine demand, and (3) these effects are consistent across all phases of the estrous cycle.

Background Successful long-term recovery from opioid use disorder (OUD) requires continuous lapse risk monitoring and appropriate use and adaptation of recovery-supportive behaviors as lapse risk changes. Available treatments often fail to support long-term recovery by failing to account for the dynamic nature of long-term recovery. Objective The aim of this protocol paper is to describe research that aims to develop a highly contextualized lapse risk prediction model that forecasts the ongoing probability of lapse. Methods The participants will include 480 US adults in their first year of recovery from OUD. Participants will report lapses and provide data relevant to lapse risk for a year with a digital therapeutic smartphone app through both self-report and passive personal sensing methods (eg, cellular communications and geolocation). The lapse risk prediction model will be developed using contemporary rigorous machine learning methods that optimize prediction in new data. Results The National Institute of Drug Abuse funded this project (R01DA047315) on July 18, 2019 with a funding period from August 1, 2019 to June 30, 2024. The University of Wisconsin-Madison Health Sciences Institutional Review Board approved this project on July 9, 2019. Pilot enrollment began on April 16, 2021. Full enrollment began in September 2021. Conclusions The model that will be developed in this project could support long-term recovery from OUD—for example, by enabling just-in-time interventions within digital therapeutics. International Registered Report Identifier (IRRID) DERR1-10.2196/29563

Exercise is associated with lower rates of drug use in human populations and decreases drug self-administration in laboratory animals. Most of the existing literature examining the link between exercise and drug use has focused on chronic, long-term exercise, and very few studies have examined the link between exercise output (i.e., amount of exercise) and drug self-administration. The purpose of this study was to examine the effects of acute bouts of exercise on cocaine self-administration, and to determine whether these effects were dependent on exercise output and the time interval between exercise and drug self-administration. Female rats were trained to run in automated running wheels, implanted with intravenous catheters, and allowed to self-administer cocaine on a fixed ratio (FR1) schedule of reinforcement. Immediately prior to each test session, subjects engaged in acute bouts of exercise in which they ran for 0, 30, or 60 min at 12 m/min. Acute bouts of exercise before test sessions decreased cocaine self-administration in an output-dependent manner, with the greatest reduction in cocaine intake observed in the 60-min exercise condition. Exercise did not reduce cocaine self-administration when wheel running and test sessions were separated by 12 hours, and exercise did not reduce responding maintained by food or responding during a saline substitution test. These data indicate that acute bouts of exercise decrease cocaine self-administration in a time- and output-dependent manner. These results also add to a growing body of literature suggesting that physical activity may be an effective component of drug abuse treatment programs.