Cannabinoid Type 1 Receptors in the Basolateral Amygdala Regulate ACPA-Induced Place Preference and Anxiolytic-Like Behaviors

The number of cannabis users is increasing in the world. However, the mechanisms involved in the psychiatric effects and addiction formation remain unclear. Medical treatments against cannabis addiction have not yet been established. Δ9-Tetrahydrocannabinol (THC), the main active substance in cannabis, binds and affects cannabinoid type 1 receptors (CB1R) in the brain. The mice were intraperitoneally (i.p.) administered arachidonylcyclopropylamide (ACPA), a CB1R-selective agonist, and then two behavioral experiments on anxiety and addiction were performed. Administration of ACPA caused anxiolytic-like behavior in the elevated plus maze test. In addition, ACPA increased place preference in a conditioned place preference (CPP) test. The basolateral amygdala (BLA), which is the focus of this study, is involved in anxiety-like behavior and reward and is reported to express high levels of CB1R. We aimed to reveal the role of CB1R in BLA for ACPA-induced behavior. 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. These results suggest that CB1R in the BLA contributes to behavior disorders caused by the acute or chronic use of cannabis.