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

Abstract

RationaleThe 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. ObjectivesThe 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. MethodsIn 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. ResultsResults 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. ConclusionsThe present findings suggest that the ECS within the NAc shell modulates anxiety-like behaviors via FAAH and CB1R activity.