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Stress-Induced Cocaine Seeking Requires A Beta-2 Adrenergic Receptor-Regulated Pathway From The Ventral Bed Nucleus Of The Stria Terminalis That Regulates Crf Actions In The Ventral Tegmental Area, Oliver Vranjkovic, Paul J. Gasser, Clayton H. Gerndt, David A. Baker, John R. Mantsch

Biomedical Sciences Faculty Research and Publications

The ventral bed nucleus of the stria terminalis (vBNST) has been implicated in stress-induced cocaine use. Here we demonstrate that, in the vBNST, corticotropin releasing factor (CRF) is expressed in neurons that innervate the ventral tegmental area (VTA), a site where the CRF receptor antagonist antalarmin prevents the reinstatement of cocaine seeking by a stressor, intermittent footshock, following intravenous self-administration in rats. The vBNST receives dense noradrenergic innervation and expresses β adrenergic receptors (ARs). Footshock-induced reinstatement was prevented by bilateral intra-vBNST injection of the β-2 AR antagonist, ICI-118,551, but not the β-1 AR antagonist, betaxolol. Moreover, bilateral intra-vBNST injection of …

Neurobiological Mechanisms That Contribute To Stress-Related Cocaine Use, John R. Mantsch, Oliver Vranjkovic, Robert C. Twining, Paul J. Gasser, Jayme R. Mcreynolds, Jordan M. Blacktop

Biomedical Sciences Faculty Research and Publications

The ability of stressful life events to trigger drug use is particularly problematic for the management of cocaine addiction due to the unpredictable and often uncontrollable nature of stress. For this reason, understanding the neurobiological processes that contribute to stress-related drug use is important for the development of new and more effective treatment strategies aimed at minimizing the role of stress in the addiction cycle. In this review we discuss the neurocircuitry that has been implicated in stress-induced drug use with an emphasis on corticotropin releasing factor actions in the ventral tegmental area (VTA) and an important pathway from the …

Stressor- And Corticotropin Releasing Factor-Induced Reinstatement And Active Stress-Related Behavioral Responses Are Augmented Following Long-Access Cocaine Self-Administration By Rats, John R. Mantsch, David A. Baker, David M. Francis, Eric S. Katz, Michael A. Hoks, Joseph P. Serge

Biomedical Sciences Faculty Research and Publications

Rationale Stressful events during periods of drug abstinence likely contribute to relapse in cocaine-dependent individuals. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) responsiveness.

Objectives This study examined stressor- and CRF-induced cocaine seeking and other stress-related behaviors in rats with different histories of cocaine self-administration (SA).

Materials and methods Rats self-administered cocaine under short-access (ShA; 2 h daily) or long-access (LgA; 6 h daily) conditions for 14 days or were provided access to saline and were tested for reinstatement by a stressor (electric footshock), cocaine or an icv injection of CRF and …

Restraint-Induced Corticosterone Secretion And Hypothalamic Crh Mrna Expression Are Augmented During Acute Withdrawal From Chronic Cocaine Administration, John R. Mantsch, Sarah Taves, Tayyiba Khan, Eric S. Katz, Tanveer Sajan, Lee C. Tang, William E. Cullinan, Dana R. Ziegler

Biomedical Sciences Faculty Research and Publications

Stress responses during cocaine withdrawal likely contribute to drug relapse and may be intensified as a consequence of prior cocaine use. The present study examined changes in stressor-induced activation of the hypothalamic–pituitary–adrenal (HPA) axis during acute withdrawal from chronic cocaine administration. Adult male Sprague–Dawley rats received daily administration of cocaine (30 mg/kg, i.p.) or saline for 14 days. Twenty-four hours after the last injection, rats in each group were sacrificed under stress-free conditions or following 30 min of immobilization. Plasma corticosterone (CORT) was measured in trunk-blood using radioimmunoassay, corticotropin-releasing hormone (CRH) mRNA levels in the paraventricularnucleus (PVN) of the hypothalamus …