Naltrexone alters the processing of social and emotional stimuli in healthy adults

Abstract

Endogenous opioids have complex social effects that may depend on specific receptor actions and vary depending on the "stage" of social behavior (e.g., seeking vs. responding to social stimuli). We tested the effects of a nonspecific opioid antagonist, naltrexone (NTX), on social processing in humans. NTX is used to treat alcohol and opiate dependence, and may affect both mu and kappa-opioid systems. We assessed attention ("seeking"), and subjective and psychophysiological responses ("responding") to positive and negative social stimuli. Based on literature suggesting mu-opioid blockade impairs positive social responses, we hypothesized that NTX would decrease responses to positive social stimuli. We also tested responses to negative stimuli, which might be either increased by NTX's mu-opioid effects or decreased by its kappa-opioid effects. Thirty-four healthy volunteers received placebo, 25 mg, or 50 mg NTX across three sessions under double-blind conditions. At each session, participants completed measures of attention, identification, and emotional responses for emotional faces and scenes. NTX increased attention to emotional expressions, slowed identification of sadness and fear, and decreased ratings of arousal for social and nonsocial emotional scenes. These findings are more consistent with anxiolytic kappa-antagonist than mu-blocking effects, suggesting effects on kappa receptors may contribute to the clinical effects of NTX.

Keywords: Naltrexone; emotion perception; opiate system; psychophysiology; social processes.

Conflict of interest statement

statement No potential conflict of interest was reported by the authors.

Figures

Figure 1

NTX increased self-reports of feeling a drug effect (“Feel Drug”) and disliking the drug effect (“Dislike Drug”) on the DEQ (top panel and middle panel), and self-reports of Fatigue on the POMS (bottom panel). Of note, some subjective effects of NTX were significantly evident both before and after the social processing tasks, although subjective effects generally appear to have peaked after the social processing tasks. *p < .05 difference between 50 mg NTX and placebo, +p < .05 difference between 25 mg NTX and placebo.

Figure 2

NTX (50 mg) increased initial attention, measured as initial direction of gaze, to emotional faces (vs. neutral faces) regardless of the emotion displayed. *p < .05 difference between 50 mg NTX and placebo.

Figure 3

NTX (50 mg) increased the intensity required for identification of sad and fearful emotional expressions without significantly affecting identification of happy expressions. *p < .05 difference between 50 mg NTX and placebo.

Figure 4

NTX (50 mg) marginally decreased ratings of arousal for all types of emotional pictures, regardless of social vs. nonsocial content. #p = .06 difference between 50 mg NTX and placebo.