Dual role of nitrergic neurotransmission in the bed nucleus of the stria terminalis in controlling cardiovascular responses to emotional stress in rats

Abstract

These results indicate that inhibitory control of stress-evoked cardiovascular responses by nitrergic signalling in the BNST is mediated by a facilitation of local noradrenergic neurotransmission. The present data also provide evidence of an involvement of local nNOS in facilitatory control of tachycardia during stress by NMDA receptors within the BNST.

Cannabinoid receptor type 1 in the bed nucleus of the stria terminalis modulates cardiovascular responses to stress via local N-methyl-D-aspartate receptor/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling

“…Activation of the NMDA glutamatergic receptor in postsynaptic neurons results in NO formation through a Ca +2 -dependent mechanism and activation of the nNOS (Chachlaki and Prevot, 2019; Garthwaite, 2008, 2019). Accordingly, we recently reported that the facilitatory influence of the NMDA receptor within the BNST in stress-evoked cardiovascular responses is mediated by local nNOS activation (Barretto-de-Souza et al, 2018). Although these pieces of evidence, the endocannabinoid-glutamate neurotransmission interaction was never explored in terms of an involvement of NO signaling.…”

“…The aim of this experiment was to investigate the involvement of local NMDA glutamate receptor, nNOS, sGC, and PKG in control of the cardiovascular responses to acute restraint stress by the CB 1 receptor within the BNST. For this, independent sets of rats were pretreated into the BNST with either the selective NMDA receptor antagonist LY235959 (0.5 nmol/100 nL), the selective nNOS inhibitor NPLA (0.2 nmol/100 nL), the sGC inhibitor ODQ (0.5 nmol/100 nL), the selective PKG inhibitor KT5823 (0.01 nmol/100 nL/side), or vehicle (saline or DMSO 20%, 100 nL/side) (Barretto-de-Souza et al, 2018; Oliveira et al, 2018). Five minutes later, the animals received either vehicle (DMSO 20%, 100 nL/side) or AM251 (100 pmol/100 nL) into the BNST (Gomes-de-Souza et al, 2016).…”

“…Previous studies reported that the CB 1 receptor acts presynaptically, inhibiting local glutamatergic inputs within the BNST (Centanni et al, 2019; Glangetas et al, 2013; Lange et al, 2017; Massi et al, 2008; Puente et al, 2010). In this sense, a facilitatory influence of the N-methyl-D-aspartate (NMDA) receptor within the BNST in the control of cardiovascular responses during aversive threats was reported (Adami et al, 2017; Barretto-de-Souza et al, 2018; Hott et al, 2017). Taken together, these results support the hypothesis that the inhibitory influence of BNST endocannabinoid neurotransmission in the control of cardiovascular responses to restraint stress might be mediated by an inhibition of local glutamatergic neurotransmission.…”

“…Activation of the NMDA glutamate receptor is the best characterized mechanism for activation of the neuronal isoform of the neuronal nitric oxide synthase (nNOS) enzyme in the brain (Chachlaki and Prevot, 2019; Garthwaite, 2008, 2019). Accordingly, a recent study identified that control of cardiovascular responses to restraint stress by NMDA receptor in the BNST is mediated by activation of local nNOS (Barretto-de-Souza et al, 2018). Nevertheless, although reports of interaction between endocannabinoid and glutamatergic neurotransmissions within the BNST (Centanni et al, 2019; Glangetas et al, 2013; Massi et al, 2008; Puente et al, 2010), an interaction between endocannabinoid and nitrergic neurotransmission has never been reported.…”

Role of the Bed Nucleus of the Stria Terminalis in PTSD: Insights From Preclinical Models

“…Adami et al (2017) showed that, after restraint, BNST glutamatergic neurotransmission in rodents influences changes in heart rate and tail skin temperature via co-activation of N-Methyl-D-aspartate (NMDA) and non-N-Methyl-D-aspartate (NMDA) receptors. Several studies have also demonstrated an involvement of CRF1 and CRF2 receptors (Oliveira et al, 2015), α1-adrenoceptors (Barretto-de-Souza et al, 2018), and endocannabinoid CB1 receptors (Gomes-de-Souza et al, 2016) in the BNST in cardiovascular adjustments during restraint stress (Oliveira et al, 2015). However, PVN CRF mRNA is not upregulated following restraint stress (Stroth et al, 2011) indicating upstream activation of CRF function ( via PACAP, for example; Hammack et al, 2010; King et al, 2017b).…”