Age-Dependent Differences in Cerebellar CB1 Receptor Expression and Its Association With Impulsivity and Alcohol Intake in Rats

Abstract

The cannabinoid receptor 1 (CB1R) in the hippocampus has been involved in impulsivity and alcohol consumption in adolescent rats. However, the role of CB1R in the cerebellum, despite that structure's exceptionally high CB1R density, remains unexplored. We therefore tested the hypothesis that cerebellar CB1R contributes to regulating impulsive behaviour, alcohol consumption and seeking. Male Wistar rats, adolescent (PND25), adult (PND90) and aged (PND365), were assessed on the delay discounting task (DDT) and for voluntary alcohol intake-conditioned place preference (ACPP). CB1R levels were quantified via immunofluorescence in the CRUS II and interposed nucleus. Separate cohorts were used for voluntary alcohol consumption and alcohol-conditioned place preference (ACPP). Results showed that adolescent rats displayed significantly greater impulsivity and alcohol consumption than adults and aged rats, and only adolescents developed ACPP. CB1R expression peaked in adolescents across both cerebellar regions, but only Crus II levels correlated positively with impulsivity (k value), indicating a region- and age-specific contribution. These data reveal, for the first time, that CB1R in cerebellar Crus II selectively underpins adolescent impulsive choice and alcohol consumption and seeking, highlighting both a novel brain locus and a critical developmental window for endocannabinoid modulation. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.