Wickensonn Norzé, Astrid Ramos, Amanda Rodriguez, Paola Eusebio,Valeria Schleier, Alexander Acevedo, Kristie

Torres, Keimarie Berrios, Isabel Castellano, and Carmen S Maldonado-Vlaar.

University of Puerto Rico Rio Piedras, Department of Biology, PO BOX 23360, San Juan, Puerto Rico.

Clinical studies provide strong evidence that stress is an environmental risk factor that can trigger the onset of several neuropsychiatric disorders such as anxiety and depression in humans. Preclinical evidence suggests that the endocannabinoid and endovanilloid systems within the brain are important neuronal substrates involved in emotional responses to stress. Specifically, studies have proposed that the Transient Receptor Potential Vanilloid 1 (TRPV1), a member of the Transient Receptor Potential (TRP) superfamily, within the brain regulate anxiety and depression behaviors through its interactions with the cannabinoid receptor 1 (CB1R). However, little is known about the cellular mechanisms that regulate these receptors’ interactions across the brain and their impact on neuropsychiatric disorders. We investigated the role of TRVP1 and CB1R within several brain regions, including the medial prefrontal cortex as part of the dopamine mesocorticolimbic system, the hippocampus, and the amygdala in anxiety and depression like-behaviors using rats as animal models. To examine the role of these two receptors in depression like-behaviors, male and female Sprague Dawley rats were treated for 4 days with vehicle or FAAH inhibitor URB597 [ 0; 0.1;0.2mg/kg.ip] 2 hours before testing in the forced swim test (FST) for 6 min. Another group were treated for 4 days with either vehicle or Olvanil, a TRPV1 receptor inhibitor [0; 0.3; 0.5 mg/kg/ip] 30 min before testing in the FST for 6 min, a third group of animals were treated for 4 days with either vehicle or URB597 [0; 0.1 ;0.2mg/kg.ip] and Olvanil [0; 0.3; 0.5 mg/kg/ip] 2 hours before testing in the FST for 6 min. Floating and swimming behaviors were observed during the FST session. Our results suggest that URB597 significantly decreased depression like-behavior. In contrast, treatment with olvanil increased depression-like behaviors in the experimental animals when compared to controls. Dual treatment of experimental compounds decreased depression likebehaviors. Ongoing biochemical analysis of the changes in expression of TRPV1 and CB1 receptors following treatment with URB597 and olvanil will support mechanistic explanations for the present behavioral results.


CB1 receptors, TRPV1 receptors, Anxiety, Depression, Endocannabinoids

Funding support:

This research was supported by NIDA, Grant# 1R15 DA044500-01A1 to CS Maldonado Vlaar,

No financial interests or potential conflicts of interests have biased these studies.

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