Adolescent CB1 receptor antagonism influences subsequent social interactions and neural activity in female rats
The endogenous cannabinoid system (ECS), which consists of endocannabinoids - signalling lipid molecules, cannabinoid receptors CB1 and CB2 that they bind to, and enzymes that metabolize and transport them, has recently emerged as a likely regulator of social interaction development in adolescents. In a recent study, scientists investigated the effects of CB1 receptor function on social development and identified candidate brain regions involved in these effects in rat model animals.
Towards the first goal, male and female rats were treated daily with a CB1 receptor inhibitor in their adolescent period and then tested in a social interaction paradigm after a 5-day drug washout period, which coincided with their adulthood. The researchers found that inhibition of the brain’s CB1 receptor during adolescence leads to a later increase in social interactions in female rats but not in males.
To address the second goal, the researchers repeated the drug treatment and social interaction tests at similar time points on another cohort of female rats. The rats’ brains were then collected to measure neural activation in various regions of the hippocampus and the medial prefrontal cortex in the brain, which have been known to play important roles in rewards associated with social interactions. Data indicated that female rats treated with a CB1 inhibitor had increased neural activity in the nucleus accumbens shell and cingulate gyrus of the medial prefrontal cortex.
Together, these results demonstrate a sex-specific role of adolescent endocannabinoid signalling in the development of social behaviours and suggest brain regions likely involved in the CB1-mediated increases in social interactions, especially in female. These findings also highlight that adolescence is a period vulnerable to long-term impacts of cannabis and similar compounds usage due to altered endocannabinoid signalling.