Involvement of endocannabinoid neurotransmission in the bed nucleus of stria terminalis in cardiovascular responses to acute restraint stress in rats

Abstract

Graduate Program in Physiological Sciences, São Carlos, SP, Brazil BACKGROUND AND PURPOSEEndocannabinoid signalling has been reported as an important neurochemical mechanism involved in responses to stress. Previous studies provided evidence of endocannabinoid release in the bed nucleus of the stria terminalis (BNST) during aversive stimuli. Nevertheless, a possible involvement of this neurochemical mechanism in stress responses has never been evaluated. Therefore, in the present study we investigated the involvement of BNST endocannabinoid neurotransmission, acting via local CB 1 receptors, in the cardiovascular responses to acute restraint stress in rats. EXPERIMENTAL APPROACHThe selective CB 1 receptor antagonist AM251 (1, 30 and 100 pmol 100 nL À1 ) and/or the fatty acid amide hydrolase (FAAH) enzyme inhibitor URB597 (30 pmol 100 nL À1 ) or the monoacylglycerol lipase (MAGL) enzyme inhibitor JZL184 (30 pmol 100 nL À1 ) was microinjected into the BNST before the acute restraint stress. KEY RESULTSMicroinjection of AM251 into the BNST enhanced the tachycardia caused by restraint stress, without affecting the increase in arterial pressure and the sympathetic-mediated cutaneous vasoconstrictor response. Conversely, the increased endogenous levels of AEA in the BNST evoked by local treatment with the FAAH enzyme inhibitor URB597 decreased restraint-evoked tachycardia. Inhibition of the hydrolysis of 2-arachidonoylglycerol (2-AG) in the BNST by local microinjection of the MAGL enzyme inhibitor JZL184 also decreased the HR response. These effects of URB597 and JZL184 were abolished by BNST pretreatment with AM251. CONCLUSIONS AND IMPLICATIONSThese findings indicate an involvement of BNST endocannabinoid neurotransmission, acting via CB 1 receptors, in cardiovascular adjustments during emotional stress, which may be mediated by the local release of either AEA or 2-AG.Abbreviations 2-AG, 2-arachidonoylglycerol; AEA, anandamide or arachidonoylethanolamide; BNST, bed nucleus of the stria terminalis; CBD, cannabidiol; CRF, corticotropin-releasing factor; DBP, diastolic blood pressure; FAAH, fatty acid amide hydrolase; HR, heart rate; MAGL, monoacylglycerol lipase; MBP, mean blood pressure; MPFC, medial prefrontal cortex; NTS, nucleus of the solitary tract; PAG, periaqueductal gray; PVN, hypothalamic paraventricular nucleus; RVLM, rostral ventrolateral medulla; TRPV1, transient receptor potential vanilloid 1; Δ 9 -THC, Δ 9 -tetrahydrocannabinol

Chronic Ethanol Vapor Exposure Potentiates the Cardiovascular Responses to Acute Stress in Male but Not in Female Rats

“…Our ndings are in line with previous studies that reported blood pressure and HR increases and decrease in the skin temperature as physiological changes during restraint stress [10,16,18,19,[66][67][68]. However, differently from other authors [22,23], we did not observe an in uence of sex on MAP and HR during the stress session.…”

“…The cutaneous temperature of the tail was recorded using a thermal camera (IRI4010, InfraRed Integrated Systems Ltd., Northampton, UK). The temperature was measured on ve points of the animal's tail and the mean value was calculated for each recording [19,54].…”

“…Cardiovascular recording of MAP and HR of freely moving rats began at least 30 min before the onset of the restraint, and was performed throughout the session of stress. The tail skin temperature was measured 10, 5 and 0 min before the restraint for baseline values, and at 5, 10, 15, 20, 25 and 30 min during restraint [16,19]. At the end of the experiment, the rats were anesthetized with iso urane inhalation and decapitated.…”

“…This model is characterized by unconditioned and unavoidable stress-elicited neuroendocrine and cardiovascular responses, the latter being characterized by sustained blood pressure and heart rate (HR) increases that last throughout the restraint period [10,15,16]. In addition, cutaneous vasoconstriction during restraint leads to a fall in the tail skin temperature [17][18][19].…”

Participação do sistema endocanabinóide no núcleo leito da estria terminal sobre respostas de ansiedade em ratos

“…Poucos trabalhos na literatura descrevem o papel do sistema endocanabinoide presente no NLET sobre as resposta de medo condicionado (Gomes et al, 2012;Gomes-de-Souza et al, 2016;Lange et al, 2016;Massi et al, 2008;Puente et al, 2010;Resstel et al, 2008a). Entretanto, já foi demonstrada a influência dessa estrutura sobre a resposta emocional condicionada (REC).…”