Sexual dimorphic distribution of cannabinoid 1 receptor mRNA in adult C57BL/6J mice

The cannabinoid 1 receptor (CB₁R) is the most abundant G protein-coupled receptor in the brain and plays crucial roles in emotion and behavior by modulating or mediating synaptic transmission and plasticity. Differences in CB₁R density between male and female rodents may be associated with distinct behavioral phenotypes. In the rat brain, CB₁R expression is significantly lower in the prefrontal cortex and amygdala of estrus females than in males. However, differences in CB₁R distribution due to sex over the whole mouse brain are still largely unknown. Here, we systemically investigated the expression of CB₁R mRNA in the brains of both male and female adult C57BL/6J mice using fluorescence in situ hybridization. There were significantly more CB₁R positive cells in males than in females in the orbital cortex, insular cortex, cingulate cortex, piriform cortex, secondary visual cortex, caudate putamen (striatum), and ventral hippocampal CA1. There were significantly more CB₁R mRNA cells in females than males in the fornix and dorsal hypothalamus. However, in some regions, strong hybridization signals without sex differences were detected, such as in the motor cortex, septum, medial habenular nucleus, and inferior colliculus. Moreover, female mice displayed different CB₁R mRNA expression patterns in the medial amygdala, basolateral amygdala, and parabrachial nucleus during different phases of the estrous cycle. These findings provide a basis for understanding sexual dimorphism in physiological and pathological brain functions related to CB₁R.