The ventromedial prefrontal cortex (vmPFC) has been shown to negatively regulate cocaine-seeking behavior, but the precise conditions by which vmPFC activity can be exploited to reduce cocaine relapse are currently unknown. We used viral-mediated gene transfer of designer receptors (DREADDs) to activate vmPFC neurons and examine the consequences on cocaine seeking in a rat self-administration model of relapse. Activation of vmPFC neurons with the Gq-DREADD reduced reinstatement of cocaine seeking elicited by cocaineassociated cues, but not by cocaine itself. We used a retro-DREADD approach to confine the Gq-DREADD to vmPFC neurons that project to the medial nucleus accumbens shell, confirming that these neurons are responsible for the decreased cue-induced reinstatement of cocaine seeking. The effects of vmPFC activation on cue-induced reinstatement depended on prior extinction training, consistent with the reported role of this structure in extinction memory. These data help define the conditions under which chemogenetic activation of extinction neural circuits can be exploited to reduce relapse triggered by reminder cues.

Posttraumatic stress disorder (PTSD) and alcohol use disorders (AUD) are two of the most common mental health disorders affecting civilians as well as military populations. If left untreated, individuals with co-occurring PTSD/AUD are at increased risk for developing other mental health problems (e.g., depression, anxiety), physical health problems, reduced resiliency and military readiness, and vocational and social impairment. Substantial gaps in the treatment of co-occurring PTSD/AUD exist and there is a critical need to develop more effective pharmacological treatments. The current study addresses this gap in the literature by testing the efficacy and safety of doxazosin, a long-acting and selective alpha-1 adrenergic antagonist, as compared to placebo in reducing PTSD and AUD severity among U.S. military veterans. Noradrenergic dysregulation has been implicated in the development and maintenance of PTSD and AUD, and pilot studies examining doxazosin in PTSD-only or AUD-only samples have shown promise. This is the first study, however, to evaluate doxazosin in a comorbid PTSD/AUD sample. This paper describes the rationale, design and methodology of a randomized, double-blind, placebo-controlled trial of doxazosin (16 mg/day) delivered over 12 weeks among military veterans with current PTSD and AUD. In addition, functional magnetic resonance imaging (fMRI) is applied at pre- and post-treatment to investigate the underlying pathophysiology of comorbid PTSD/AUD and identify prognostic indicators of treatment outcome. This study is designed to accelerate research on co-occurring PTSD/AUD and provide empirical evidence to inform clinical practice.

Alcohol's effects on bystander responses to potential sexual assault situations are understudied. In this mixed-methods study, we examined quality of bystander responses in intoxicated versus sober people. Participants were 121 young adults (ages 21–29, 50% female) randomly assigned to consume alcoholic beverages or soda water. After drinking, participants listened to a sexual assault vignette and completed a semistructured interview assessing how they would respond if they had witnessed the situation. Nearly all participants reported they would directly intervene if faced with the situation. Intoxicated participants and men were significantly less likely to use high-quality bystander intervention strategies than were sober participants and women. Results suggest that alcohol intoxication may negatively impact the likelihood that bystander intervention efforts will be helpful.

Background and Objectives Prescription opioid (PO) use disorder is a national public health crisis. Distress tolerance and alexithymia are two separate but related components of emotion regulation that are known to impact substance use disorders. No studies to date, however, have examined the role of distress tolerance and alexithymia in PO use disorder. Thus, the current study examined the association between distress tolerance, alexithymia, and specific motivations for PO use. Methods Participants were non‐treatment‐seeking individuals with current PO use disorder (N = 81; average age = 35.0). Assessments included the Distress Tolerance Scale, Toronto Alexithymia Scale, and the Inventory of Drug Taking Situations. Results The findings indicate that distress tolerance mediated the association between alexithymia and PO use in negative situations. Specifically, distress tolerance mediated the association between alexithymia and unpleasant emotions, testing personal control, and conflict with others. Conclusions and Scientific Significance The results provide novel information regarding emotional states that may contribute to PO use and are malleable intervention targets. Additionally, this study adds to existing literature exploring the relationship between distress tolerance and substance use and is the first to expand upon the connection between alexithymia and distress tolerance in an opioid‐using population. Implications for clinical practice and future research are discussed.