title: Effects of the CRF1 antagonist antalarmin on cocaine self-administration and discrimination in rhesus monkeys.
abstract: Cocaine stimulates the rapid release of ACTH, and by inference, CRF in several species, suggesting that the HPA "stress" axis may contribute to the abuse-related effects of cocaine. The effects of a systemically-active CRF(1) receptor antagonist, antalarmin, on cocaine self-administration and cocaine discrimination were examined in rhesus monkeys. Antalarmin's acute (1-10 mg/kg, IV) and chronic (3.2 mg/kg IV) effects on IV cocaine self-administration were studied. The acute effects of 3.2 mg/kg IV antalarmin on the cocaine self-administration dose-effect curve (0.001-0.10 mg/kg/inj) were also examined. The acute effects of antalarmin (5 and 10 mg/kg, IM) on the cocaine discrimination dose-effect curve (0.013-1.3 mg/kg) were examined. Antalarmin did not significantly decrease the reinforcing or the discriminative stimulus effects of cocaine. Acute antalarmin administration produced a dose-dependent but non-significant decrease in self-administration of 0.01 mg/kg/inj cocaine but did not alter the cocaine dose-effect curve. Chronic daily antalarmin treatment did not significantly decrease cocaine-maintained responding. Antalarmin did not significantly alter either the cocaine discrimination dose-effect curve or the time course of the cocaine-training dose. Antalarmin (10 mg/kg) produced sedation, suggesting that it was centrally active, however, it did not attenuate cocaine's abuse-related effects in rhesus monkeys.
authors.affiliation: Alcohol and Drug Abuse Research Center, McLean Hospital, 115 Mill Street, Belmont, MA 02478 USA. mello@mclean.harvard.edu
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Mello
authors.forename: S Stevens
authors.initials: SS
authors.lastname: Negus
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.forename: Jack H
authors.initials: JH
authors.lastname: Mendelson
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D004192:Discrimination, Psychological / Q000187:drug effects*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008253:Macaca mulatta; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D012646:Self Administration
chemical_list: D011743:Pyrimidines; D011758:Pyrroles; C103016:antalarmin; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine