Individual Vulnerability to Stress Is Associated With Increased Demand for Intravenous Heroin Self-administration in Rats

• Published in: Frontiers in behavioral neuroscience Vol. 13; p. 134
• Main Authors: Stafford, Nathaniel P., Kazan, Theodore N., Donovan, Colleen M., Hart, Erin E., Drugan, Robert C., Charntikov, Sergios
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 25.06.2019; Frontiers Media S.A
• Subjects: Addictions; Addictive behaviors; Animal cognition; Anxiety; Behavior; Biomarkers; Cocaine; Comorbidity; Corticosterone; Drug self-administration; economic demand; Exploration; Extinction behavior; Heroin; heroin demand; Intravenous administration; Narcotics; Neuroscience; Opioids; Post traumatic stress disorder; Psychopharmacology; Reinstatement; Risk factors; Social research; stress; swim-stress; Swimming; Trauma; Yohimbine; United States > US; stress; post-traumatic stress disorder; heroin; swim-stress; economic demand; cue reinstatement; heroin demand; stress reinstatement
• ISSN: 1662-5153; 1662-5153
• DOI: 10.3389/fnbeh.2019.00134

Opioid use is a widespread epidemic, and traumatic stress exposure is a critical risk factor in opioid use and relapse. There is a significant gap in our understanding of how stress contributes to heroin use, and there are limited studies investigating individual differences underlying stress reactivity and subsequent stress-induced heroin self-administration. We hypothesized that greater individual vulnerability to stress would predict higher demand for heroin self-administration in a within-subjects rodent model of stress and heroin use comorbidity. Male rats were exposed to inescapable intermittent swim stress (ISS) and individual biological (corticosterone) or behavioral [open field, social exploration, and forced swim tests (FSTs)] measures were assessed before and after the stress episode. Individual demand for self-administered heroin (0.05 mg/kg/infusion; 12-h sessions) was assessed using a behavioral economics approach followed by extinction and reinstatement tests triggered by stress re-exposure, non-contingent cue presentations, and yohimbine (0, 1.0, or 2.5 mg/kg). We found that behavioral, biological, and a combination of behavioral and biological markers sampled prior to and after the stress episode that occurred weeks before the access to heroin self-administration predicted the magnitude of individual demand for heroin. Non-contingent presentation of cues, that were previously associated with heroin, reinstated heroin seeking in extinction. For the first time, we show that individual biological response to an ecologically relevant stressor in combination with associated behavioral markers can be used to predict subsequent economic demand for heroin.