Brain-wide mapping reveals temporal and sexually dimorphic opioid actions

Area of Science:

• Neuroscience
• Pharmacology
• Neuroanatomy

Background:

• Opioid mechanisms and brain region targeting are unclear.
• Sex differences in opioid responses lack anatomical basis.

Purpose of the Study:

• Develop an automated whole-brain mapping method for neuronal activity.
• Investigate time- and sex-dependent brain activation by morphine.

Main Methods:

• Used ribbon scanning confocal microscopy for whole-brain imaging.
• Analyzed c-Fos expression in male and female mice at 1 and 4 hours post-morphine.
• Developed a scalable and unbiased approach for anatomical mapping.

Main Results:

• Distinct patterns of morphine-induced brain activation observed across time and sex.
• More significant activity differences found at 4 hours versus 1 hour.
• Males showed changes in dopamine system; females showed changes in cortical regions.

Conclusions:

• The developed approach offers comprehensive insights into drug-of-abuse effects on the brain.
• Reveals sex-specific and time-dependent neuroanatomical alterations following opioid exposure.
• Highlights the importance of considering sex and time in opioid research.