Medial prefrontal cortex endocannabinoid system modulates baroreflex activity through CB₁receptors

Abstract

[481][482][483][484][485][486][487][488] 2006) have shown that glutamatergic synapses in the ventral portion of the medial prefrontal cortex (vMPFC) modulate baroreflex activity. Moreover, glutamatergic neurotransmission in the vMPFC can be modulated by the endocannabinoids system (eCBs), particularly the endocannabinoid anandamide, through presynaptic CB 1 receptor activation. Therefore, in the present study, we investigated eCBs receptors that are present in the vMPFC, and more specifically whether CB1 receptors modulate baroreflex activity. We found that bilateral microinjection of the CB 1 receptor antagonist AM251 (100 or 300 pmol/200 nl) into the vMPFC increased baroreflex activity in unanesthetized rats. Moreover, bilateral microinjection of either the anandamide transporter inhibitor AM404 (100 pmol/200 nl) or the inhibitor of the enzyme fatty acid amide hydrolase that degrades anandamide, URB597 (100 pmol/200 nl), into the MPFC decreased baroreflex activity. Finally, pretreatment of the vMPFC with an ineffective dose of AM251 (10 pmol/200 nl) was able to block baroreflex effects of both AM404 and URB597. Taken together, our results support the view that the eCBs in the vMPFC is involved in the modulation of baroreflex activity through the activation of CB1 receptors, which modulate local glutamate release.anandamide; autonomic system; cannabinoids; infralimbic cortex; prelimbic cortex THE MEDIAL PREFRONTAL CORTEX (MPFC) is a limbic structure that is involved in the modulation of autonomic responses exerting influence on the cardiovascular system in rats (44, 57). The ventral portion of the MPFC (vMPFC), which is compounded by the infralimbic (IL), prelimbic (PL), and dorsal peduncular cortexes (41, 61), is involved in the modulation of baroreflex activity (49,56).Glutamatergic terminals and ionotropic glutamate receptors were reported in the vMPFC of rats (18,36). Furthermore, a previous study from our group showed that local injection of L-glutamate into the vMPFC evokes an activation of both sympathetic and parasympathetic activities on the heart of unanesthetized rats (48). Moreover, the glutamatergic system present in the vMPFC is involved in baroreflex modulation (45).In the central nervous system (CNS), the endocannabinoid anandamide is synthesized on demand in postsynaptic neurons, after calcium influx increase (13,42). Anandamide immediately diffuses to the synaptic cleft, activating CB 1 cannabinoid receptors, which are located in presynaptic terminals (59). The action of anandamide is limited by its reuptake through a putative anandamide transporter, being subsequently metabolized by the intracellular enzyme fatty acid amide hydrolase (FAAH) that is located in postsynaptic neurons (14, 43). These two mechanisms, which cooperate to attenuate anandamide signaling in the CNS, can be pharmacologically inhibited by drugs such as AM404 (anandamide re-uptake inhibitor) and URB597 (FAAH inhibitor).The CB 1 cannabinoid receptor is one of the most abundant G protein-coupled receptors in the brain and ...

Medial prefrontal cortex N-methyl-D-aspartate receptor/nitric oxide/cyclic guanosine monophosphate pathway modulates both tachycardic and bradycardic baroreflex responses

“…CB1 receptors are located presynaptically in glutamatergic neuron terminations within the vMPFC (Devane et al, 1988), where they can modulate glutamate release (Auclair et al, 2000). Moreover, recent work from our group has shown that activation of vMPFC CB1 receptors decreases both cardiac baroreflex bradycardic and tachycardic responses (Ferreira-Junior et al, 2012), i.e., an effect opposite to that observed with stimulation of the glutamatergic system (Resstel and Correa, 2006c), which suggests that the vMPFC endocannabinoid system can influence baroreflex activity probably by modulating glutamate release. However, the role of vMPFC NMDA receptors in the cardiac sympathetic component of the baroreflex was not investigated.…”

Effect of angiotensin II on voltage-gated sodium currents in aortic baroreceptor neurons and arterial baroreflex sensitivity in heart failure rats

“…Moreover, some studies have already demonstrated that Ang II blunts the arterial baroreflex sensitivity[14, 17]. The arterial baroreflex sensitivity is usually evaluated by reflex changes of heart rate in response to changes in arterial blood pressure, namely the arterial baroreflex control of heart rate[18, 19]. To further explore the mechanisms about blunted arterial baroreflex sensitivity in the CHF state, the first aim in this study was to test whether the regulatory effect of Ang II on the aortic baroreceptor neurons contributes to the deficiency in the arterial baroreflex control of heart rate in CHF.…”

Hippocampal subareas arranged in the dorsoventral axis modulate cardiac baroreflex function in a site‐dependent manner in rats

“…The MPFC is a region that sends projections to brainstem areas related to cardiovascular tonic control (Fisk & Wyss, 2000;Vertes, 2004). Furthermore, the MPFC modulates baroreflex function (Ferreira-Junior et al 2012, 2013. Therefore, the MPFC may be a part of the neural circuitry that allows the VH to modulate cardiac baroreflex function.…”

“…Linear regression was generated matching induced mean arterial pressure (MAP) variations with reflex HR responses. Paired values of MAP ( MAP) and HR ( HR) variations were plotted to create the linear regression for each rat, and their slopes were compared to test changes in baroreflex gain (Ferreira-Junior et al 2012). We have used linear regression to analyse either bradycardia or tachycardia responses separately (Alves et al 2009a).…”

“…Several studies have shown that forebrain areas, such as the medial prefrontal cortex (MPFC), bed nucleus of stria terminalis (BNST), hypothalamus and amygdala, can modulate baroreflex function (Crestani et al 2008(Crestani et al , 2010aFerreira-Junior et al 2012;Fortaleza et al 2015). The baroreflex is responsible for maintaining BP at homeostatic levels (Guyenet, 2006).…”