Regulatory system of cannabinoid type 1 receptors in the basolateral amygdala on the place preference and anxiolytic-like behaviors

Cannabis is the most widely used addictive drug following alcohol and tobacco. However, the mechanisms involved in the mental effects and dependence formation are unclear. Δ9-tetrahydrocannabinol (THC), the main active substance in cannabis, binds and affects cannabinoid type 1 receptors (CB1R) in the brain. The mice were i.p. administered arachidonylcyclopropylamide (ACPA), a CB1R-selective agonist, and then two behavioral experiments were performed. Treatments of ACPA induced the anxiolytic-like behavior in the elevated plus maze test. ACPA increased place preference in the conditioned place preference test. The BLA of mice highly expresses CB1R in the GABAergic interneurons. We aimed to reveal the role of CB1R in BLA for ACPA-induced behaviors. AM251, a CB1R selective antagonist, was administered intra-BLA before i.p. administration of ACPA. Intra-BLA administration of AM251 inhibited ACPA-induced anxiolytic-like behavior and place preference. Furthermore, in vivo microdialysis was performed to measure basal GABA levels in the BLA. Acute administration of ACPA had significantly increased basal GABA levels. Chronic administration of ACPA did't affect basal GABA levels. These results suggest that CB1R in the BLA contributes to behavior disorders caused by the acute or chronic use of cannabis and these behaviors maight be through a complex control system involving GABA. This study suggests that CB1R in the BLA may lead to new therapeutic targets in the treatment of cannabis-induced adverse effects.