BACKGROUND: Positively reinforcing properties of alcohol are in part mediated by activation of the ventral striatum (VS). Alcohol-induced release of endogenous opioids is thought to contribute to this response. Preclinical studies show that the opioid antagonist naltrexone (NTX) can block this cascade, but its ability to do so in treatment-seeking alcoholics has not been examined. Our objective was to study the effects of NTX on alcohol-induced VS activation and on amygdala response to affective stimuli in treatment-seeking alcohol-dependent inpatients. METHODS:Sixty-three treatment-seeking alcoholics were randomized to receive NTX (50 mg) or placebo (PLC) daily. On Day 7, participants underwent an alcohol cue reactivity session, and craving was measured using the Penn Alcohol Craving Scale. On Day 9, participants received a saline infusion followed by an alcohol infusion and also viewed affective stimuli in a magnetic resonance scanner. RESULTS: Irrespective of medication treatment condition, the alcohol infusion did not activate the VS in the alcohol-dependent patients. Unexpectedly, VS activation was greater in NTX treated patients than in the PLC group. NTX treated patients also reported increased craving in response to alcohol cue exposure, and increased subjective response to alcohol ("high" and "intoxicated") compared to PLC subjects. No significant effects of alcohol infusion on brain response to affective stimuli were in the NTX or PLC groups. CONCLUSIONS: Unlike previous findings in social drinkers, a moderate level of intoxication did not activate the VS in treatment-seeking alcoholics. This is likely to reflect tolerance to the positively reinforcing properties of alcohol in this clinical population. Our findings may help explain the efficacy of NTX to reduce heavy drinking, but not to maintain abstinence. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
RCT Entities:
BACKGROUND: Positively reinforcing properties of alcohol are in part mediated by activation of the ventral striatum (VS). Alcohol-induced release of endogenous opioids is thought to contribute to this response. Preclinical studies show that the opioid antagonist naltrexone (NTX) can block this cascade, but its ability to do so in treatment-seeking alcoholics has not been examined. Our objective was to study the effects of NTX on alcohol-induced VS activation and on amygdala response to affective stimuli in treatment-seeking alcohol-dependent inpatients. METHODS: Sixty-three treatment-seeking alcoholics were randomized to receive NTX (50 mg) or placebo (PLC) daily. On Day 7, participants underwent an alcohol cue reactivity session, and craving was measured using the Penn Alcohol Craving Scale. On Day 9, participants received a saline infusion followed by an alcohol infusion and also viewed affective stimuli in a magnetic resonance scanner. RESULTS: Irrespective of medication treatment condition, the alcohol infusion did not activate the VS in the alcohol-dependent patients. Unexpectedly, VS activation was greater in NTX treated patients than in the PLC group. NTX treated patients also reported increased craving in response to alcohol cue exposure, and increased subjective response to alcohol ("high" and "intoxicated") compared to PLC subjects. No significant effects of alcohol infusion on brain response to affective stimuli were in the NTX or PLC groups. CONCLUSIONS: Unlike previous findings in social drinkers, a moderate level of intoxication did not activate the VS in treatment-seeking alcoholics. This is likely to reflect tolerance to the positively reinforcing properties of alcohol in this clinical population. Our findings may help explain the efficacy of NTX to reduce heavy drinking, but not to maintain abstinence. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Authors: A J Roberts; J S McDonald; C J Heyser; B L Kieffer; H W Matthes; G F Koob; L H Gold Journal: J Pharmacol Exp Ther Date: 2000-06 Impact factor: 4.030
Authors: Milky Kohno; Laura E Dennis; Holly McCready; Daniel L Schwartz; William F Hoffman; P Todd Korthuis Journal: Drug Alcohol Depend Date: 2018-09-21 Impact factor: 4.492
Authors: Amanda Elton; Samantha Dove; Cory N Spencer; Donita L Robinson; Charlotte A Boettiger Journal: Alcohol Clin Exp Res Date: 2019-04-08 Impact factor: 3.455
Authors: Derik Hermann; Natalie Hirth; Matthias Reimold; Anil Batra; Michael N Smolka; Sabine Hoffmann; Falk Kiefer; Hamid R Noori; Wolfgang H Sommer; Gerald Reischl; Christian la Fougère; Karl Mann; Rainer Spanagel; Anita C Hansson Journal: Neuropsychopharmacology Date: 2016-08-11 Impact factor: 7.853
Authors: Aaron C Lim; Dara G Ghahremani; Erica N Grodin; ReJoyce Green; Spencer Bujarski; Emily E Hartwell; Kelly E Courtney; Kent Hutchison; Karen Miotto; Lara A Ray Journal: Drug Alcohol Depend Date: 2019-05-09 Impact factor: 4.852
Authors: Andrea King; Ashley Vena; Deborah S Hasin; Harriet deWit; Sean J O'Connor; Dingcai Cao Journal: Am J Psychiatry Date: 2021-01-05 Impact factor: 19.242
Authors: Melissa A Cyders; Martin H Plawecki; William Corbin; Andrea King; Denis M McCarthy; Vijay A Ramchandani; Jessica Weafer; Sean J O'Connor Journal: Alcohol Clin Exp Res Date: 2020-03-15 Impact factor: 3.455
Authors: Lara A Ray; Erica N Grodin; Lorenzo Leggio; Anita J Bechtholt; Howard Becker; Sarah W Feldstein Ewing; James David Jentsch; Andrea C King; Barbara J Mason; Stephanie O'Malley; James MacKillop; Markus Heilig; George F Koob Journal: Addict Biol Date: 2020-04-14 Impact factor: 4.280