Drug addiction is a chronic disorder characterized by high rates of relapse, even after long periods of abstinence from drug use. Similarly, long-term success of dietary treatments is low because most individuals relapse to unhealthy eating habits within months of starting treatment. Therefore, investigations into the environmental factors and neural mechanisms that increase one's vulnerability to relapse are critical to the development of novel treatment strategies for these major public health problems. Although chronic stress has long been associated with relapse vulnerability in the clinical literature, relatively few pre-clinical studies have used models of relapse that incorporate a chronic stressor. During the current funding period, we added a chronic stress component to two widely used animal models of craving and relapse: the extinction/reinstatement model and the related forced abstinence model. We showed that animals with a history of chronic stress displayed greater relapse to drug and food seeking compared to unstressed rats for up to 1 week following the termination of stress. We also demonstrated that systemic dopamine D1-like receptor antagonism during chronic stress attenuated the effects of the stress on subsequent relapse-like behavior. Building on these findings, Aim 1 will determine the effects of chronic stress on relapse to cocaine and palatable food seeking following punishment-induced (self-imposed) abstinence. This model captures the human situation in which abstinence is self-imposed due to the negative consequences of continued seeking or use, and therefore, may have a translational advantage.
Aim 2 will determine the anatomical location of chronic stress' dopaminergic mechanism by targeting discrete regions of medial prefrontal cortex with the selective D1-like receptor antagonist SCH-39166. Along with identifying the environmental and neuropharmacological determinants of relapse to cocaine and palatable food seeking as a means to inform novel treatment strategies, these studies will provide undergraduate students with meaningful, hands-on research experiences, thereby enhancing the research environment at Bloomsburg University.

Public Health Relevance

The overarching goal of the proposed research is to study the effects of chronic stress on subsequent relapse to cocaine and palatable food seeking. Successful completion of this project will show that chronic stress increases vulnerability to relapse after voluntary abstinence and that this effect is mediated by dopamine D1-like receptors in medial prefrontal cortex. Elucidation of such mechanisms is critical to the development of improved strategies for the treatment of both drug addiction and unhealthy eating habits.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Academic Research Enhancement Awards (AREA) (R15)
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Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
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Kautz, Mary A
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Bloomsburg University of Pennsylvania
Schools of Arts and Sciences
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Ball, Kevin T; Stone, Eric; Best, Olivia et al. (2018) Chronic restraint stress during withdrawal increases vulnerability to drug priming-induced cocaine seeking via a dopamine D1-like receptor-mediated mechanism. Drug Alcohol Depend 187:327-334
Ball, Kevin T; Best, Olivia; Luo, Jonathan et al. (2017) Chronic restraint stress causes a delayed increase in responding for palatable food cues during forced abstinence via a dopamine D1-like receptor-mediated mechanism. Behav Brain Res 319:1-8
Ball, Kevin T; Miller, Leah; Sullivan, Christopher et al. (2016) Effects of repeated yohimbine administration on reinstatement of palatable food seeking: involvement of dopamine D1 -like receptors and food-associated cues. Addict Biol 21:1140-1150
Ball, Kevin T; Jarsocrak, Hanna; Hyacinthe, Johanna et al. (2015) Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine. Behav Brain Res 294:1-6
Ball, Kevin T; Slane, Mylissa (2014) Tolerance to the locomotor-activating effects of 3,4-methylenedioxymethamphetamine (MDMA) predicts escalation of MDMA self-administration and cue-induced reinstatement of MDMA seeking in rats. Behav Brain Res 274:143-8
Ball, Kevin T; Slane, Mylissa (2012) Differential involvement of prelimbic and infralimbic medial prefrontal cortex in discrete cue-induced reinstatement of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats. Psychopharmacology (Berl) 224:377-85
Ball, Kevin T; Klein, Jessalyn E; Plocinski, Jacob A et al. (2011) Behavioral sensitization to 3,4-methylenedioxymethamphetamine is long-lasting and modulated by the context of drug administration. Behav Pharmacol 22:847-50