Mitchell Jennifer M, Tavares Venessa C, Fields Howard L, D'Esposito Mark, Boettiger Charlotte A
Ernest Gallo Clinic and Research Center, University of California at San Francisco, Emeryville, CA 94608, USA.
Neuropsychopharmacology. 2007 Feb;32(2):439-49. doi: 10.1038/sj.npp.1301226. Epub 2006 Oct 18.
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.
阿片受体拮抗剂纳曲酮（NTX）是少数几种被批准用于治疗酒精成瘾的药物之一，但其减少饮酒的机制尚不清楚。在大鼠中，NTX可减少吗啡诱导的冲动选择偏差；然而，对于该药物对人类冲动行为的离散方面（如决策和抑制控制）的影响却一无所知。在此，我们使用一种改良的延迟折扣程序来研究NTX是否能改善人类的决策或抑制控制。我们测量了急性NTX（50毫克）对一组戒酒者（AA）和健康对照者（CS）在较小即时（SS）和较大延迟金钱奖励之间的选择以及在高冲突条件下的反应错误（运动不匹配）的影响。我们之前报道过，在这个范式中，AA比CS更频繁地选择SS选项。如果AA的选择偏差是由于对潜在奖励的内源性阿片信号增强所致，那么NTX应该会减少AA组中的这种偏差。我们发现NTX并不能可靠地减少AA组中的冲动选择；然而，NTX对个体间选择偏差的影响是可以可靠预测的。NTX对选择偏差的影响与罗特控制点（LOC）量表的得分显著相关；越来越偏向内控的LOC得分预示着在NTX作用下冲动选择的可能性增加。此外，我们发现NTX显著增强了对运动反应的控制，尤其是在CS组中。这些结果表明，内源性阿片类物质可能会在冲突情境下的决策过程中损害反应选择，并且NTX对明确决策的影响取决于个体性格。确定这种依赖性的生物学基础可能对有效的酒精成瘾治疗具有重要意义。
