title: Corticotropin-releasing factor-1 receptor antagonists decrease heroin self-administration in long- but not short-access rats.
abstract: 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.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, USA.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Greenwell
authors.forename: Cindy K
authors.initials: CK
authors.lastname: Funk
authors.forename: Pietro
authors.initials: P
authors.lastname: Cottone
authors.forename: Heather N
authors.initials: HN
authors.lastname: Richardson
authors.forename: Scott A
authors.initials: SA
authors.lastname: Chen
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.forename: Eric P
authors.initials: EP
authors.lastname: Zorrilla
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D006556:Heroin Dependence / Q000517:prevention & control*; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012646:Self Administration; D013997:Time Factors; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology*; D000099052:CRF Receptor, Type 1
chemical_list: C476980:MJL 1-109-2; D011743:Pyrimidines; C412383:R 121919; D018019:Receptors, Corticotropin-Releasing Hormone; D014227:Triazines; D000099052:CRF Receptor, Type 1