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

Abstract

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.

Insular cortex corticotropin-releasing factor integrates stress signaling with social decision making

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Comparison of cannabidiol to citalopram in targeting fear memory in female mice

“…Therefore, our results suggest a sexual dimorphism in the effect of CBD on contextual memory in mice. This is consistent with well documented sexual dimorphisms in contextual fear memory processing in general (Cossio et al 2016;Farrell et al 2013;Jasnow et al 2006;Kobayashi et al 2020;Dalla et al 2009), and noted sexual dimorphisms in the distribution and function of the major receptor signaling pathways that support CBD signaling in rodents (Jimenez Naranjo et al 2019;Liu et al 2020;Inoue et al 2014;Uphouse et al 1991;Greaves et al 2005). This result could be important for guiding the design and interpretation of fear memory experiments involving mixed genders and could have clinical relevance as discussed below.…”

Spontaneous Mouse Behavior in Presence of Dissonance and Acoustic Roughness

“…Sexual differences at the circuit level could also be involved. For example, recent work showed a sexual dimorphic distribution of cannabinoid receptor mRNA in the brains of C57BL/6J mice ( Liu et al, 2020 ), a receptor that is linked to emotional modulation and anxiety-like behavior in rodents and humans ( Akirav, 2011 ; Bowers and Ressler, 2016 ), two features which influence sensory perception.…”