Imaging Sex Differences in Regional Brain Metabolism during Acute Opioid Withdrawal

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.