Thibaut R Pardo-García1, Nadira Yusif-Rodriguez2, Guillermo Yudowski3, Carmen S Maldonado-Vlaar4. 1. University of Puerto Rico-Rio Piedras Campus, Department of Biology, PO Box 23360, San Juan, 00931, Puerto Rico. Electronic address: trpg@umich.edu. 2. University of Puerto Rico-Rio Piedras Campus, Department of Biology, PO Box 23360, San Juan, 00931, Puerto Rico. Electronic address: nadira_yusif_rodriguez@brown.edu. 3. University of Puerto Rico-Medical School, Institute of Neurobiology, San Juan, 00936, Puerto Rico. 4. University of Puerto Rico-Rio Piedras Campus, Department of Biology, PO Box 23360, San Juan, 00931, Puerto Rico. Electronic address: carmen.maldonado7@upr.edu.
Abstract
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.
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.
Authors: Steven G Kinsey; Scott T O'Neal; Jonathan Z Long; Benjamin F Cravatt; Aron H Lichtman Journal: Pharmacol Biochem Behav Date: 2010-12-08 Impact factor: 3.533
Authors: Tim V Salomons; Robin Nusslock; Allison Detloff; Tom Johnstone; Richard J Davidson Journal: J Cogn Neurosci Date: 2015-02 Impact factor: 3.225