Rimonabant reveals reward- and anxiety-related behavioral effects of N-arachidonoyl dopamine (N-ADA) in mice

The endovanilloid N-arachidonoyl dopamine (N-ADA) is a lipid mediator associated with nociception and inflammation, but its effects on reward and anxiety remain unclear. We examined the behavioral impact of subacute N-ADA pre-exposure on conditioned place preference (CPP) and anxiety-like behavior in the circular open-field test (COF), assessed both under basal conditions and after acute CB1 blockade/GPR55 modulation with rimonabant. Male BALB/c mice were pre-exposed for four days to either vehicle (10% ethanol) or N-ADA (0.1 mg/kg). A counterbalanced CPP protocol was then conducted over eight days. Place preference was assessed before and after rimonabant administration (0.1 mg/kg), and anxiety-like behavior was evaluated using the COF following rimonabant. N-ADA exposure alone did not significantly modify place preference compared to baseline (p > 0.05). However, following rimonabant administration, N-ADA-exposed mice displayed a significant increase in preference for the drug-paired compartment (p < 0.05) and increased anxiety-like behavior in the COF (p < 0.05). These findings indicate that prior exposure to N-ADA can influence reward- and anxiety-related behaviors specifically under conditions of CB1 blockade/GPR55 modulation. The results support the modulatory role of N-ADA on reward- and anxiety-related behaviors at the dose tested, indicating an interaction with endocannabinoid signaling (or other rimonabant-sensitive mechanisms).