Open AccessEvaluation of mifepristone effects on alcohol-seeking and self-administration in baboons.
Author(s) -
August F. Holtyn,
Elise M. Weerts
Publication year - 2019
Publication title -
experimental and clinical psychopharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.066
H-Index - 92
eISSN - 1936-2293
pISSN - 1064-1297
DOI - 10.1037/pha0000246
Subject(s) - mifepristone , administration (probate law) , self administration , alcohol , psychology , medicine , anesthesia , clinical psychology , pharmacology , social psychology , psychotherapist , political science , pregnancy , biology , biochemistry , genetics , law
Mifepristone, a type II glucocorticoid receptor antagonist, is under investigation as a potential pharmacotherapy for alcohol use disorder. This study examined effects of chronic administration of mifepristone on alcohol-seeking and self-administration in large nonhuman primates. Adult baboons ( n = 5) self-administered alcohol 7 days/week under a chained schedule of reinforcement (CSR). The CSR comprised 3 components in which distinct cues were paired with different schedule requirements, with alcohol available for self-administration only in the final component, to model different phases of alcohol anticipation, seeking, and consumption. Under baseline conditions, baboons self-administered an average of 1g/kg/day of alcohol in the self-administration period. Mifepristone (10, 20, and 30 mg/kg) or vehicle was administered orally 30 min before each CSR session for 7 consecutive days. In a separate group of baboons ( n = 5) acute doses of mifepristone (10, 20, and 30 mg/kg) were administered, and blood samples were collected over 72 hr to examine mifepristone pharmacokinetics. Some samples also were collected from the baboons that self-administered alcohol under the CSR after the chronic mifepristone condition. Mifepristone did not alter alcohol-seeking or self-administration under the CSR when compared with the vehicle condition. Mifepristone pharmacokinetics were nonlinear, and appear to be capacity limited. In sum, mifepristone did not reduce alcohol-maintained behaviors when administered to baboons drinking 1g/kg daily. (PsycINFO Database Record (c) 2019 APA, all rights reserved).