Journal
ADDICTION BIOLOGY
Volume 14, Issue 2, Pages 130-143Publisher
WILEY
DOI: 10.1111/j.1369-1600.2008.00142.x
Keywords
Addiction; antagonist; CRF; escalation; heroin; self-administration
Categories
Funding
- National Institutes of Health [DA04043, DA019295]
- National Institute on Drug Abuse [DK64871]
- National Institute of Diabetes and Digestive and Kidney Diseases
- University of Rome La Sapienza
- The Scripps Research Institute [18771]
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Dysregulation of the stress-related corticotropin-releasing factor (CRF) system has been implicated in the development of drug dependence. The present study examined the effects of administering CRF type 1 (CRF1) receptor antagonists on heroin self-administration in animals allowed short (1 hour) or long (8-12 hours) access to intravenous heroin self-administration sessions. The nonpeptide CRF1 antagonists MJL-1-109-2 (1 hour versus 8 hours access) or R121919 (1 hour versus 12 hours access) were systemically injected in both short- and long-access rats. MJL-1-109-2 (10 mg/kg) and R121919 (10 and 20 mg/kg) reduced heroin self-administration in long-access animals without altering heroin intake in short-access animals. Both MJL-1-109-2 and R121919 decreased first-hour intravenous heroin self-administration selectively in long-access rats, with R121919 decreasing cumulative heroin intake across the 12-hour session. The results demonstrate that blockade of the CRF-CRF1 receptor system attenuates the increased heroin intake of rats with extended access to the drug.
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