Exposure to stressful events during withdrawal from psychostimulants, such as cocaine or amphetamine, induces drug craving and drug relapse in both animal models and human individuals. The effects of stress on drug-seeking behavior persist for months following psychostimulant abstinence, and play a large part in chronic relapses associated with psychostimulant addiction. It is the chronic nature of psychostimulant addiction and relapse that produces significant social, health and economic impact. Identifying the neurological alterations that occur during psychostimulant withdrawal will have significant impact on the development of pharmacological treatments designed to prevent drug relapse. The studies outlined by this proposal will determine whether psychostimulant abuse results in increased sensitivity of stress-related neural systems. These studies will also establish the duration of these effects during psychostimulant withdrawal. This will be achieved by using laboratory rat models of psychostimulant withdrawal. Changes in stress behavior, and alterations to the activity of neurotransmitter systems that regulate stress behavior, will be determined during acute and protracted withdrawal from amphetamine. Furthermore, studies will determine whether alterations to neural stress systems and stress behavior following psychostimulant withdrawal can be reversed by chronic treatment of the antidepressant, fluoxetine. Together, the proposed experiments will elucidate the neural substrates of stress sensitivity during psychostimulant withdrawal, and will determine the feasibility of antidepressant treatment to reduce stress behaviors and thus psychostimulant relapse.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Pilotte, Nancy S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of South Dakota
Other Basic Sciences
Schools of Medicine
United States
Zip Code
Weber, Matthew A; Graack, Eric T; Scholl, Jamie L et al. (2018) Enhanced dopamine D2 autoreceptor function in the adult prefrontal cortex contributes to dopamine hypoactivity following adolescent social stress. Eur J Neurosci 48:1833-1850
Forster, Gina L; Anderson, Eden M; Scholl, Jamie L et al. (2018) Negative consequences of early-life adversity on substance use as mediated by corticotropin-releasing factor modulation of serotonin activity. Neurobiol Stress 9:29-39
Luo, Jialie; Feng, Jing; Yu, Guang et al. (2018) Transient receptor potential vanilloid 4-expressing macrophages and keratinocytes contribute differentially to allergic and nonallergic chronic itch. J Allergy Clin Immunol 141:608-619.e7
Hemmings, Sian M J; Malan-Müller, Stefanie; van den Heuvel, Leigh L et al. (2017) The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study. Psychosom Med 79:936-946
Watt, Michael J; Weber, Matthew A; Davies, Shaydel R et al. (2017) Impact of juvenile chronic stress on adult cortico-accumbal function: Implications for cognition and addiction. Prog Neuropsychopharmacol Biol Psychiatry 79:136-154
Solanki, Rajeshwari R; Scholl, Jamie L; Watt, Michael J et al. (2016) Amphetamine Withdrawal Differentially Increases the Expression of Organic Cation Transporter 3 and Serotonin Transporter in Limbic Brain Regions. J Exp Neurosci 10:93-100
Novick, Andrew M; Mears, Mackenzie; Forster, Gina L et al. (2016) Adolescent social defeat alters N-methyl-D-aspartic acid receptor expression and impairs fear learning in adulthood. Behav Brain Res 304:51-9
Lowry, Christopher A; Smith, David G; Siebler, Philip H et al. (2016) The Microbiota, Immunoregulation, and Mental Health: Implications for Public Health. Curr Environ Health Rep 3:270-86
Bray, Brenna; Scholl, Jamie L; Tu, Wenyu et al. (2016) Amphetamine withdrawal differentially affects hippocampal and peripheral corticosterone levels in response to stress. Brain Res 1644:278-87
Stamper, Christopher E; Hennessey, Patrick A; Hale, Matthew W et al. (2015) Role of the dorsomedial hypothalamus in glucocorticoid-mediated feedback inhibition of the hypothalamic-pituitary-adrenal axis. Stress 18:76-87

Showing the most recent 10 out of 55 publications