Medical College of Wisconsin
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Neurobiological mechanisms underlying relapse to cocaine use: contributions of CRF and noradrenergic systems and regulation by glucocorticoids. Stress 2014 Jan;17(1):22-38



Pubmed ID




Scopus ID

2-s2.0-84890909066   26 Citations


Considering its pervasive and uncontrollable influence in drug addicts, understanding the neurobiological processes through which stress contributes to drug use is a critical goal for addiction researchers and will likely be important for the development of effective medications aimed at relapse prevention. In this paper, we review work from our laboratory and others focused on determining the neurobiological mechanisms that underlie and contribute to stress-induced relapse of cocaine use with an emphasis on the actions of corticotropin-releasing factor in the ventral tegmental area (VTA) and a key pathway from the bed nucleus of the stria terminalis to the VTA that is regulated by norepinephrine and beta adrenergic receptors. Additionally, we discuss work suggesting that the influence of stress in cocaine addiction changes and intensifies with repeated cocaine use in an intake-dependent manner and examine the potential role of glucocorticoid hormones in the underlying drug-induced neuroadaptations. It is our hope that research in this area will inform clinical practice and medication development aimed at minimizing the contribution of stress to the addiction cycle, thereby improving treatment outcomes and reducing the societal costs of addiction.

Author List

McReynolds JR, Peña DF, Blacktop JM, Mantsch JR


John Mantsch PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenergic Neurons
Behavior, Addictive
Cocaine-Related Disorders
Conditioning, Operant
Corticotropin-Releasing Hormone
Models, Animal
Neuronal Plasticity
Prefrontal Cortex
Secondary Prevention
Self Administration
Septal Nuclei
Stress Disorders, Post-Traumatic
Stress, Psychological
Ventral Tegmental Area