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PRECLINICAL STUDY: Corticotropin‐releasing factor‐1 receptor antagonists decrease heroin self‐administration in long‐ but not short‐access rats
Author(s) -
Greenwell Thomas N.,
Funk Cindy K.,
Cottone Pietro,
Richardson Heather N.,
Chen Scott A.,
Rice Kenner C.,
Zorrilla Eric P.,
Koob George F.
Publication year - 2009
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/j.1369-1600.2008.00142.x
Subject(s) - heroin , self administration , medicine , pharmacology , endocrinology , systemic administration , drug administration , drug , biology , microbiology and biotechnology , in vivo
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 (CRF 1 ) 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 CRF 1 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–CRF 1 receptor system attenuates the increased heroin intake of rats with extended access to the drug.