Augmented Cocaine Seeking in Response to Stress or CRF Delivered into the Ventral Tegmental Area Following Long-Access Self-Administration Is Mediated by CRF Receptor Type 1 But Not CRF Receptor Type 2

Authors

Jordan M. Blacktop, Marquette University
Chad Seubert, Marquette University
David A. Baker, Marquette UniversityFollow
Nathan Ferda, Marquette University
Geng Lee, Marquette University
Evan N. Graf, Marquette UniversityFollow
John R. Mantsch, Marquette UniversityFollow

Document Type

Article

Language

eng

Format of Original

8 p.

Publication Date

8-2011

Publisher

Society for Neuroscience

Source Publication

The Journal of Neuroscience

Source ISSN

0270-6474

Original Item ID

doi: 10.1523/JNEUROSCI.1393-11.2011

Abstract

Stressful events are determinants of relapse in recovering cocaine addicts. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) regulation of neurocircuitry involved in drug seeking. We previously reported that the reinstatement of cocaine seeking by a stressor (footshock) is CRF dependent and is augmented in rats that self-administered cocaine under long-access (LgA; 6 h daily) conditions for 14 d when compared with rats provided shorter daily cocaine access [short access (ShA) rats; 2 h daily]. Further, we have demonstrated that reinstatement in response to intracerebroventricular CRF administration is heightened in LgA rats. This study examined the role of altered ventral tegmental area (VTA) responsiveness to CRF in intake-dependent increases in CRF- and stress-induced cocaine seeking. Bilateral intra-VTA administration of CRF (250 or 500 ng/side) produced reinstatement in LgA but not ShA rats. In LgA rats, intra-VTA CRF-induced reinstatement was blocked by administration of the CRF-receptor type 1 (CRF-R1) antagonist antalarmin (500 ng/side) or CP-376395 (500 ng/side), but not the CRF-R2 antagonist astressin-2B (500 ng or 1 μg/side) or antisauvagine-30(ASV-30; 500 ng/side) into the VTA. Likewise, intra-VTA antalarmin, but not astressin-2B, blocked footshock-induced reinstatement in LgA rats. By contrast, neither intra-VTA antalarmin nor CP-376395 altered food-reinforced lever pressing. Intra-VTA injection of the CRF-R1-selective agonist cortagine (100 ng/side) but not the CRF-R2-selective agonist rat urocortin II (rUCN II; 250 ng/side) produced reinstatement. These findings reveal that excessive cocaine use increases susceptibility to stressor-induced relapse in part by augmenting CRF-R1-dependent regulation of addiction-related neurocircuitry in the VTA.

Comments

Published version. Journal of Neuroscience, Vol. 31, No. 31, (Aug 3, 2011): 11396-11403. DOI. © 2011 Society for Neuroscience. Used with permission.

Recommended Citation

Blacktop, Jordan M.; Seubert, Chad; Baker, David A.; Ferda, Nathan; Lee, Geng; Graf, Evan N.; and Mantsch, John R., "Augmented Cocaine Seeking in Response to Stress or CRF Delivered into the Ventral Tegmental Area Following Long-Access Self-Administration Is Mediated by CRF Receptor Type 1 But Not CRF Receptor Type 2" (2011). Biomedical Sciences Faculty Research and Publications. 3.
https://epublications.marquette.edu/biomedsci_fac/3