# Brain-wide mapping reveals temporal and sexually dimorphic opioid actions

## TL;DR

This study maps brain activity in mice after morphine exposure, showing differences over time and between sexes.

## Contribution

A scalable workflow for whole-brain mapping reveals sex- and time-dependent opioid effects in mice.

## Key findings

- Morphine induces distinct brain activation patterns across time and sex in mice.
- Male mice showed higher c-Fos expression in several brain regions compared to females.
- The workflow can be used to study spatiotemporal drug effects on neuronal activity.

## Abstract

The field of neuroscience has been transformed by recent advances in spatial mapping of neuronal activity across whole cleared brains. Rapid adoption of these techniques requires computational workflows that can facilitate experiments comparing multiple conditions across large cohorts of individuals. We therefore developed a scalable approach for anatomical mapping of c-Fos positive cells in whole brain and applied it to map the response to the prototypic opioid, morphine. The analysis revealed distinct patterns of morphine-induced regional brain activation across both time and sex. These results support the multi-wave model of opioid-induced brain activation. Male mice displayed higher c-Fos expression than females in several key brain regions including nucleus accumbens, central amygdalar nucleus, ventral pallidum, prelimbic area, anterior cingulate area, and olfactory tubercle. Overall, this workflow can be applied to not only examine spatiotemporal actions of drugs of abuse on neuronal activity across the brain, but also mapping neuronal activity more generally.

This study introduces a semi-automated, scalable whole-brain mapping workflow that enables unbiased comparisons across cohorts, revealing widespread temporally and sexually distinct regional activation patterns after acute morphine exposure in mice.