Opioid-blunted cortisol response to stress is associated with increased negative mood and wanting of social reward

Abstract

Animal research suggests a central role of the μ-opioid receptor (MOR) system in regulating affiliative behaviors and in mediating the stress-buffering function of social contact. However, the neurochemistry of stress-related social contact seeking in humans is still poorly understood. In a randomized, double-blind, between-subjects design, healthy female volunteers (N = 80) received either 10 mg of the µ-opioid agonist morphine sulfate, or a placebo. Following a standardized psychosocial stress induction, participants engaged in a social reward task, in which the motivation to obtain skin-to-skin social touch and the hedonic reactions elicited by such touch were assessed. Morphine prevented the increase of salivary cortisol typically observed following acute stress exposure. Notably, this altered HPA axis responsivity was associated with increased negative affect in response to psychosocial stress, and with enhanced subjective wanting of highly rewarding social contact. These findings provide novel evidence on the effect of exogenous opioids administration on the reactions to psychosocial stress and point to a state-dependent regulation of social motivation.

Opioid analgesic effects on subjective well‐being in the operating theatre*

“…Moreover, and in line with the early findings by Beecher et al. [13], increased negative affect has been reported after morphine [19], oxycodone [16] and remifentanil [20] administration. Nevertheless, opioid analgesics are routinely used clinically with the aim of dampening subjective and physiological stress, e.g.…”

“…While the opioid analgesics hydromorphone, morphine and buprenorphine have been shown to block cortisol responses to stress induction, none relieved subjective anxiety [14,15,19]. Moreover, and in line with the early findings by Beecher et al [13], increased negative affect has been reported after morphine [19], oxycodone [16] and remifentanil [20] administration.…”

“…Somewhat surprisingly, laboratory studies also indicate a lack of efficacy of opioids for relieving anxiety and other negative emotions. While the opioid analgesics hydromorphone, morphine and buprenorphine have been shown to block cortisol responses to stress induction, none relieved subjective anxiety [14, 15, 19]. Moreover, and in line with the early findings by Beecher et al.…”

Effects of dopamine and opioid receptor antagonism on the neural processing of social and nonsocial rewards

“…Finally, regardless of the drug group, in the ROI analysis we observed that wanting-related activity in the NAc and medial OFC was mainly elicited by the anticipation of food rewards, but not touch rewards, suggesting possible differences in neuroanatomical circuitry underlying social and nonsocial reward processing. Social touch is considered a reward as it triggers approach behavior (wanting)-for example, individuals are willing to work to obtain it-and its experience is commonly associated with pleasure (liking), expressed as subjective ratings or positive facial expressions (e.g., Korb, Götzendorfer, et al, 2020;Løseth et al, 2019;Massaccesi et al, 2021Massaccesi et al, , 2022Mayo et al, 2018;Perini et al, 2015).…”

“…Finally, regardless of the drug group, in the ROI analysis we observed that wanting‐related activity in the NAc and medial OFC was mainly elicited by the anticipation of food rewards, but not touch rewards, suggesting possible differences in neuroanatomical circuitry underlying social and nonsocial reward processing. Social touch is considered a reward as it triggers approach behavior (wanting)—for example, individuals are willing to work to obtain it—and its experience is commonly associated with pleasure (liking), expressed as subjective ratings or positive facial expressions (e.g., Korb, Götzendorfer, et al, 2020 ; Korb, Massaccesi, et al, 2020 ; Løseth et al, 2019 ; Massaccesi et al, 2021 , 2022 ; Mayo et al, 2018 ; Perini et al, 2015 ). Nevertheless, prior neuroimaging research showed that social touch is commonly associated with activity in the insula, secondary somatosensory cortex, and temporal regions, while activity of reward‐related brain regions, like the OFC and the NAc, has been less consistently reported (e.g., Bjornsdotter et al, 2014 ; Gordon et al, 2013 ; Sailer et al, 2016 ; Sander & Nummenmaa, 2021 ).…”