1. ¹Ernest Gallo Clinic and Research Center, University of California at San Francisco, Emeryville, CA, USA
2. ²Department of Neurology, University of California at San Francisco, San Francisco, CA, USA
3. ³Wheeler Center for the Neurobiology of Addiction, University of California at San Francisco, San Francisco, CA, USA
4. ⁴Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, CA, USA

Correspondence: Dr CA Boettiger, Ernest Gallo Clinic and Research Center, University of California at San Francisco, 5858 Horton St, Suite 200, Emeryville, CA 94608, USA. Tel: +1 510 985 3973, Fax: +1 510 985 3101; E-mail: cab@phy.ucsf.edu

Received 20 April 2006; Revised 18 July 2006; Accepted 5 September 2006; Published online 18 October 2006.

Abstract

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.