Effects of the CRF1 antagonist antalarmin on cocaine self-administration and discrimination in rhesus monkeys.
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.
Mello
Nancy K
NK
Alcohol and Drug Abuse Research Center, McLean Hospital, 115 Mill Street, Belmont, MA 02478 USA. mello@mclean.harvard.edu
Negus
S Stevens
SS
Rice
Kenner C
KC
Mendelson
Jack H
JH
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
D011743:Pyrimidines; D011758:Pyrroles; C103016:antalarmin; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine