Faculty Collaboration Database

Stressor- and corticotropin releasing factor-induced reinstatement and active stress-related behavioral responses are augmented following long-access cocaine self-administration by rats. Psychopharmacology (Berl) 2008 Jan;195(4):591-603

Date

09/28/2007

Pubmed ID

17899015

Pubmed Central ID

PMC3888801

DOI

10.1007/s00213-007-0950-5

Scopus ID

2-s2.0-36348984553 (requires institutional sign-in at Scopus site)   80 Citations

Abstract

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 for behavioral responsiveness on the elevated plus maze, in a novel environment and in the light-dark box after a 14- to 17-day extinction/withdrawal period.

RESULTS: LgA rats showed escalating patterns of cocaine SA and were more susceptible to reinstatement by cocaine, EFS, or icv CRF than ShA rats. Overall, cocaine SA increased activity in the center field of a novel environment, on the open arms of the elevated plus maze, and in the light compartment of a light-dark box. In most cases, the effects of cocaine SA were dependent on the pattern/amount of cocaine intake with statistically significant differences from saline self-administering controls only observed in LgA rats.

CONCLUSIONS: When examined after several weeks of extinction/withdrawal, cocaine SA promotes a more active pattern of behavior during times of stress that is associated with a heightened susceptibility to stressor-induced cocaine-seeking behavior and may be the consequence of augmented CRF regulation of addiction-related neurocircuitry.

Author List

Mantsch JR, Baker DA, Francis DM, Katz ES, Hoks MA, Serge JP

Author

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

Animals
Anxiety
Arousal
Cocaine
Cocaine-Related Disorders
Corticotropin-Releasing Hormone
Extinction, Psychological
Fear
Male
Maze Learning
Rats
Rats, Sprague-Dawley
Recurrence
Self Administration
Social Environment
Stress, Psychological