Blockade of the endovanilloid receptor, TRPV1, and of the endocannabinoid enzyme, FAAH, within the nucleus accumbens shell elicits anxiolytic-like effects in male rats

Rationale: The functional role of the endocannabinoid system (ECS) and Transient Receptor Potential Vanilloid type-1 (TRPV1) within the Nucleus Accumbens shell (NAc shell) remains unknown. Preclinical studies in rodents have reported that the ECS modulates emotional responses such as anxiety. The NAc shell has a high density of synaptically co-localized cannabinoid receptor type-1 (CB1R) and TRPV1, suggesting a potential involvement in the modulation of anxiety.

Objectives: The present study aims to establish the role of ECS-TRPV1 interactions within the NAc shell and its effects on anxiety. It is hypothesized that the neurochemical regulation elicited by ECS within the NAc shell mediates anxiety-like behaviors in rodents.

Methods: In this study, male Sprague Dawley rats were implanted with bilateral brain cannula targeting the NAc shell. Following recovery from surgery, animals received microinfusion pretreatments (0, 0.125, 0.5 nmol/0.4 μl) of N-arachidonoyl-serotonin (AA-5-HT), a dual blocker of the endocannabinoid-inactivating enzyme, fatty acid amide hydrolase (FAAH) and a TRPV1 antagonist in the NAc shell. Following treatment, animals were tested in an elevated plus maze (EPM) paradigm for a period of 5 minutes. At the end of the experiment, animals were sacrificed and their brains collected for histological and biochemical analysis.

Results: Results showed that animals treated with AA-5-HT in a dose dependent manner spent significantly more time in the open arms than vehicle-treated animals. In addition, AA-5-HT administration induced a significant downregulation of CB1R expression in the NAc shell.

Conclusions: The present findings suggest that the ECS within the NAc shell modulates anxiety-like behaviors via FAAH and CB1R activity.