TY - JOUR
T1 - Evaluation of mifepristone effects on alcohol-seeking and self-administration in baboons
AU - Holtyn, August F.
AU - Weerts, Elise M.
N1 - Funding Information:
This research was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award R01 AA015971. Corcept Therapeutics Incorporated gifted mifepristone and paid for independent analysis of plasma samples for the Pharmacokinetic studies. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. These funding sponsors were not involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. All authors contributed in a significant way to the manuscript and all authors have read and approved the final manuscript.
Publisher Copyright:
© 2018 American Psychological Association.
PY - 2019/6
Y1 - 2019/6
N2 - 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) selfadministered 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.
AB - 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) selfadministered 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.
KW - Alcohol
KW - Baboons
KW - Mifepristone
KW - Seeking
KW - Self-administration
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U2 - 10.1037/pha0000246.supp
DO - 10.1037/pha0000246.supp
M3 - Article
C2 - 30570274
AN - SCOPUS:85058844492
SN - 1064-1297
VL - 27
SP - 227
EP - 235
JO - Experimental and clinical psychopharmacology
JF - Experimental and clinical psychopharmacology
IS - 3
ER -