Effects of oxycodone on brain responses to emotional images

Abstract

Rationale: Evidence from animal and human studies suggests that opiate drugs decrease emotional responses to negative stimuli and increase responses to positive stimuli. Such emotional effects may motivate misuse of oxycodone (OXY), a widely abused opiate. Yet, we know little about how OXY affects neural circuits underlying emotional processing in humans.

Objective: We examined effects of OXY on brain activity during presentation of positive and negative visual emotional stimuli. We predicted that OXY would decrease amygdala activity to negative stimuli and increase ventral striatum (VS) activity to positive stimuli. Secondarily, we examined the effects of OXY on other emotional network regions on an exploratory basis.

Methods: In a three-session study, healthy adults (N = 17) received placebo, 10 and 20 mg OXY under counterbalanced, double-blind conditions. At each session, participants completed subjective and cardiovascular measures and underwent functional MRI (fMRI) scanning while completing two emotional response tasks.

Results: Our emotional tasks reliably activated emotional network areas. OXY produced subjective effects but did not alter either behavioral responses to emotional stimuli or activity in our primary areas of interest. OXY did decrease right medial orbitofrontal cortex (MOFC) responses to happy faces.

Conclusions: Contrary to our expectations, OXY did not affect behavioral or neural responses to emotional stimuli in our primary areas of interest. Further, the effects of OXY in the MOFC would be more consistent with a decrease in value for happy faces. This may indicate that healthy adults do not receive emotional benefits from opiates, or the pharmacological actions of OXY differ from other opiates.

Fig. 1

Experimental paradigms: a Emotional Pictures Task (EPT) affective images from a validated affective pictures set (Lang et al. 1999) are presented for three conditions [neutral, pleasant, unpleasant] interspersed with a variable grey fixation screen. Trials are presented for 4 s each, five times per block, two blocks per run; three runs total. b Emotional Face Matching Task (EFMT) images from a validated affective faces set (Gur et al. 2002) are presented for three conditions [two matching emotional faces (angry, fearful or happy) paired with a neutral face] interspersed with matching shapes (circle, triangle, square) paired with another shape]. Trials are presented for 5 s each, four times per block and three blocks per run per run; two runs total

Fig.2

Effects of OXY on selected subjective measures across the session ► timeline. First panel: state scale of State-Trait Anxiety Scale (STAI-S); second panel from top: Addiction Research Center Pentobarbital-Chlorpromazine-Alcohol Group (ARCI PCAG), commonly used as a measure of sedative effects; third panel: Drug Effects Questionnaire (DEQ) ratings of “I feel high”; fourth panel: Visual Analog Scale (VAS) ratings of “I feel dreamy”; fifth panel: VAS ratings of “I feel nauseated”; * p<0.05 difference 20 mg versus placebo; +p<0.05 difference 10 mg versus placebo. Error bars represent standard error of the mean (SEM)

Fig. 3

OXY (20 mg) decreased middle orbitofrontal cortex activity for happy faces, without significantly affecting activity to angry or fearful faces; *p<0.05 difference 20 mg versus placebo. Error bars represent standard error of the mean (SEM)