Endogenous opioid blockade and impulsive responding in alcoholics and healthy controls.
The opioid receptor antagonist naltrexone (NTX) is one of few approved treatments for alcoholism, yet the mechanism by which it reduces drinking remains unclear. In rats, NTX reduces morphine-induced impulsive choice bias; however, nothing is known about the drug's effect on discrete aspects of impulsive behavior in humans, such as decision-making and inhibitory control. Here, we used a modified delay discounting procedure to investigate whether NTX improves decision-making or inhibitory control in humans. We measured the effect of acute NTX (50 mg) on choice between smaller sooner (SS) and larger later monetary rewards and on response errors (motor mismatch) in a high conflict condition in a group of abstinent alcoholics (AA) and healthy control subjects (CS). We previously reported that AA selected the SS option significantly more often than did CS in this paradigm. If the choice bias of AA is due to enhanced endogenous opioid signaling in response to potential reward, NTX should reduce such bias in the AA group. We found that NTX did not reliably reduce impulsive choice in the AA group; however, NTX's effect on choice bias across individuals was robustly predictable. NTX's effect on choice bias was significantly correlated with scores on Rotter's Locus of Control (LOC) scale; increasingly internal LOC scores predicted increasing likelihood of impulsive choices on NTX. In addition, we found that NTX significantly enhanced control of motor responses, particularly within the CS group. These results suggest that endogenous opioids may impair response selection during decision-making under conflict, and that NTX's effects on explicit decision-making are personality-dependent. Determining the biological basis of this dependence could have important implications for effective alcoholism treatment.
Mitchell
Jennifer M
JM
Ernest Gallo Clinic and Research Center, University of California at San Francisco, Emeryville, CA 94608, USA.
Tavares
Venessa C
VC
Fields
Howard L
HL
D'Esposito
Mark
M
Boettiger
Charlotte A
CA
D000328:Adult; D000437:Alcoholism / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D015982:Bias; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D015984:Causality; D002492:Central Nervous System Depressants / Q000009:adverse effects; D002755:Choice Behavior / Q000187:drug effects; D003657:Decision Making / Q000187:drug effects; D004311:Double-Blind Method; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000188:drug therapy* / Q000523:psychology; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009483:Neuropsychological Tests; D018847:Opioid Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010551:Personality / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D012201:Reward; D016896:Treatment Outcome
D002492:Central Nervous System Depressants; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D000431:Ethanol; D009271:Naltrexone