Sex Differences in MOR Expression in A2 Subpopulation (2024)

Undergraduates: Nadia Velez, Lasya Kambhampati, Shriya Pokala

Faculty Advisor: Sabrina Robertson
Department: Psychology and Neuroscience

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The opioid epidemic has claimed the lives of hundreds of thousands of individuals, with opioids accounting for a significant portion of overdose-related deaths. There remains a substantial gap in our knowledge regarding the molecular mechanisms underlying sex differences observed in opioid addiction. This study aims to address this gap by focusing on mu-opioid receptor (MOR) expression in norepinephrine (NE) neurons of the A2 nucleus, a critical area implicated in stress regulation and addiction. Our hypothesis, based on existing literature indicating decreased MOR expression in female rodents in the locus coeruleus (LC), predicts a lower expression of MOR in the A2 of female mice compared to males.

Utilizing immunohistochemistry techniques, we analyzed MOR expression in genetically modified female and male mice. We precisely visualized MOR expression in the A2 NE neurons, providing a focused examination distinct from previous broad analyses of the LC. Though the A2 of female mice was observed to have lower MOR expression compared to male mice (BCF/area ratio of 2.164 vs 3.488), the difference was not statistically significant (p = 0.1511). This suggests that sex differences observed in the LC may not extend to other NE nuclei.

This study allows for greater insight into sex-specific differences in MOR and NE interaction, which can shed light on potential mechanisms contributing to opioid addiction susceptibility, particularly in females. This, in turn, can inform future therapeutic interventions targeted at addressing this pressing public health issue.