Imaging Sex Differences in Regional Brain Metabolism during Acute Opioid Withdrawal

Abstract

The rate of opioid overdose continues to rise, necessitating improved treatment options. Current therapeutic approaches rely on administration of either a blocking agent, such as naloxone, or chronic treatment with replacement drugs, including methadone and/or buprenorphine. Recent findings suggest that males and females respond to these treatments uniquely. In an effort to better understand this sex-specific variation in treatment efficacy, we investigated the effects of acute opioid withdrawal in male and female rats using 18FDG and microPET. These data demonstrate that acute opioid withdrawal produces metabolic alterations in brain regions associated with reward and drug dependence, namely corpus striatum, thalamic nuclei, septum, and frontal cortex. Furthermore, certain changes are unique to males. Specifically, males demonstrated increased metabolism in the anterior cingulate cortex and the ventral hippocampus (CA3) following acute opioid withdrawal. If males and females exhibit sex-specific changes in regional brain metabolism following acute opioid withdrawal, then perhaps it is not surprising that they respond to treatment differently.

Can neuroimaging help combat the opioid epidemic? A systematic review of clinical and pharmacological challenge fMRI studies with recommendations for future research

“…For example, estrogens can diminish opioids' antinociceptive effects [132], there is evidence of interactions and crosstalk between opioid and estrogen receptors [133], and estrogens may impact the antinociceptive and rewarding effects of methadone through effects on methadone metabolism [134]. In addition, recent preclinical work suggests sex-specific effects of acute opioid withdrawal and subsequent opioid replacement (with methadone or buprenorphine) on regional brain metabolism within regions including the anterior cingulate, amygdala and striatum [135,136]. Thus, neuroimaging studies including equal numbers of male and female participants that are specifically powered to detect sex-specific effects are urgently needed in OUD.…”