Paraventricular nucleus of the hypothalamus glutamate neurotransmission modulates autonomic, neuroendocrine and behavioral responses to acute restraint stress in rats

In the present study, the involvement of paraventricular nucleus of the hypothalamus (PVN) glutamate receptors in the modulation of autonomic (arterial blood pressure, heart rate and tail skin temperature) and neuroendocrine (plasma corticosterone) responses and behavioral consequences evoked by the acute restraint stress in rats was investigated. The bilateral microinjection of the selective non-NMDA glutamate receptor antagonist NBQX (2 nmol/ 100 nL) into the PVN reduced the arterial pressure increase as well as the fall in the tail cutaneous temperature induced by the restraint stress, without affecting the stress-induced tachycardiac response. On the other hand, the pretreatment of the PVN with the selective NMDA glutamate receptor antagonist LY235959 (2 nmol/100 nL) was able to increase the stress-evoked pressor and tachycardiac response, without affecting the fall in the cutaneous tail temperature. The treatment of the PVN with LY235959 also reduced the increase in plasma corticosterone levels during stress and inhibited the anxiogenic-like effect observed in the elevated plus-maze 24 h after the restraint session. The present results show that NMDA and non-NMDA receptors in the PVN differently modulate responses associated to stress. The PVN glutamate neurotransmission, via non-NMDA receptors, has a facilitatory influence on stress-evoked autonomic responses. On the other hand, the present data point to an inhibitory role of PVN NMDA receptors on the cardiovascular responses to stress. Moreover, our findings also indicate an involvement of PVN NMDA glutamate receptors in the mediation of the plasma corticosterone response as well as in the delayed emotional consequences induced by the restraint stress. © 2012 Elsevier B.V. and ECNP.

Control of breathing and blood pressure by parafacial neurons in conscious rats

New Findings: • What is the central question of this study? The main purpose of the present manuscript was to investigate the cardiorespiratory responses to hypoxia or hypercapnia in conscious rats submitted to neuronal blockade of the parafacial region. We clearly showed that the integrity of parafacial region is important for the respiratory responses elicited by peripheral and central chemoreflex activation in freely behavior rats. • What is the main finding and its importance? Since the parafacial region is part of the respiratory rhythm generator, they are essential for postnatal survival, which is probably due to their contribution to chemoreception in conscious rats. The retrotrapezoid nucleus (RTN), located in the parafacial region, contains glutamatergic neurons that express the transcriptor factor Phox2b and that are suggested to be central respiratory chemoreceptors. Studies in anaesthetized animals or in vitro have suggested that RTN neurons are important in the control of breathing by influencing respiratory rate, inspiratory amplitude and active expiration. However, the contribution of these neurons to cardiorespiratory control in conscious rats is not clear. Male Holtzman rats (280-300 g, n= 6-8) with bilateral stainless-steel cannulae implanted into the RTN were used. In conscious rats, the microinjection of the ionotropic glutamatergic agonist NMDA (5 pmol in 50 nl) into the RTN increased respiratory frequency (by 42%), tidal volume (by 21%), ventilation (by 68%), peak expiratory flow (by 24%) and mean arterial pressure (MAP, increased by 16 ± 4, versus saline, 3 ± 2 mmHg). Bilateral inhibition of the RTN neurons with the GABAA agonist muscimol (100 pmol in 50 nl) reduced resting ventilation (52 ± 34, versus saline, 250 ± 56 ml min-1 kg-1 with absolute values) and attenuated the respiratory response to hypercapnia and hypoxia. Muscimol injected into the RTN slightly reduced resting MAP (decreased by 13 ± 7, versus saline, increased by 3 ± 2 mmHg), without changing the effects of hypercapnia or hypoxia on MAP and heart rate. The results suggest that RTN neurons activate facilitatory mechanisms important to the control of ventilation in resting, hypoxic or hypercapnic conditions in conscious rats. © 2012 The Authors. Experimental Physiology © 2012 The Physiological Society.

Involvement of N-methyl-d-aspartate glutamate receptor and nitric oxide in cardiovascular responses to dynamic exercise in rats

Dynamic exercise evokes sustained cardiovascular responses, which are characterized by arterial pressure and heart rate increases. Although it is well accepted that there is central nervous system mediation of cardiovascular adjustments during exercise, information on the role of neural pathways and signaling mechanisms is limited. It has been reported that glutamate, by acting on NMDA receptors, evokes the release of nitric oxide through activation of neuronal nitric oxide synthase (nNOS) in the brain. In the present study, we tested the hypothesis that NMDA receptors and nNOS are involved in cardiovascular responses evoked by an acute bout of exercise on a rodent treadmill. Moreover, we investigated possible central sites mediating control of responses to exercise through the NMDA receptor-nitric oxide pathway. Intraperitoneal administration of the selective NMDA glutamate receptor antagonist dizocilpine maleate (MK-801) reduced both the arterial pressure and heart rate increase evoked by dynamic exercise. Intraperitoneal treatment with the preferential nNOS inhibitor 7-nitroindazole reduced exercise-evoked tachycardiac response without affecting the pressor response. Moreover, treadmill running increased NO formation in the medial prefrontal cortex (MPFC), bed nucleus of the stria teminalis (BNST) and periaqueductal gray (PAG), and this effect was inhibited by systemic pretreatment with MK-801. Our findings demonstrate that NMDA receptors and nNOS mediate the tachycardiac response to dynamic exercise, possibly through an NMDA receptor-NO signaling mechanism. However, NMDA receptors, but not nNOS, mediate the exercise-evoked pressor response. The present results also provide evidence that MPFC, BNST and PAG may modulate physiological adjustments during dynamic exercise through NMDA receptor-NO signaling. © 2013 Elsevier B.V.

Efeitos da injeção epidural de cetamina ou da sua associação com ifenprodil na mediação nociceptiva somática e visceral em equinos

Pós-graduação em Cirurgia Veterinária - FCAV

Identificação, purificação e determinação da estrutura e função de componentes de baixas massas moleculares do do veneno da aranha Phoneutria nigriventer (Araneae; Ctenidae)

Pós-graduação em Ciências Biológicas (Biologia Celular e Molecular) - IBRC

Cetamina S(+) como adjuvante na anestesia e no tratamento da dor pós-operatória de pacientes queimados

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Papel dos mecanismos mediados pelo fator de liberação de corticotrofina e pelo complexo receptor N-Metil-D-Aspartato-Óxido Nítrico nas reações associadas a estímulos aversivos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Citral: A monoterpene with prophylactic and therapeutic anti-nociceptive effects in experimental models of acute and chronic pain

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Phox2b-expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos de relevância versus repetição de estímulo lingüístico na indução da memória declarativa

In the LTP (Long-Term Potentiation) model of learning and memory formation, elaborated in the context of molecular neurobiology, the opening of NMDA (N-Metyl-D-Aspartate) channels to entry of calcium ions into the post-synaptic neuron depends on two excitatory events: the repeated activation of the post-synaptic neuron by only one pre-synaptic neuron (Alternative 1), or its concomitant activation by two or more pre-synaptic neurons (Alternative 2). With the purpose of testing these alternatives, in the context of Cognitive Psychology, we presented to 73 university students a sequence of slides, with the duration of 6 seconds each, containing sentences (one for each slide) considered as being relevant or irrelevant for the subjects. Relevant sentences (R1) were presented only one time, while irrelevant ones were divided in three groups: the first one with sentences presented only one time (I1), the second with sentences presented three times (I3) and the third with sentences presented five times (I5). We conjectured that relevant sentences presented only one time would mobilize two or more brain excitatory pathways (corresponding to Alternative 2 above), while repeated irrelevant sentences would progressively activate the same sensory pathway. After the presentation of the sentences, the subjects answered a written questionnaire with questions about each presented sentence. The results indicate a prevalence of correct answers to R1 over I1, I3 and I5, suggesting that the relevance factor has greater weight than repetition in the induction of declarative memories

Modulation of synaptic transmission in hippocampal CA1 neurons by a novel neurotoxin (beta-pompilidotoxin) derived from wasp venom

We examined the effects of beta-pompilidotoxin (beta-PMTX), a neurotoxin derived from wasp venom. on synaptic transmission in the mammalian central nervous system (CNS). Using hippocampal slice preparations of rodents, we made both extracellular and intracellular recordings from the CA1 pyramidal neurons in response to stimulation of the Schaffer collateral/commissural fibers. Application of 5-10 muM beta-PMTX enhanced excitatory postsynaptic potentials (EPSPs) but suppressed the fast component of the inhibitory postsynaptic potentials (IPSPs). In the presence of 10 muM bicuculline, beta-PMTX potentiated EPSPs that were composed of both non-NMDA and NMDA receptor-mediated potentials. Potentiation of EPSPs was originated by repetitive firings of the prosynaptic axons, causing Summation of EPSPs. In the presence of 10 muM CNQX and 50 muM APV, beta-PMTX suppressed GABA(A) receptor-mediated fast IPSPs but retained GABA(B) receptor-mediated slow IPSPs. Our results suggest that beta-PMTX facilitates excitatory synaptic transmission by a presynaptic mechanism and that it causes overexcitation followed by block of the activity of some population of interneurons which regulate the activity of GABA(A) receptors. (C) 2001 Published by Elsevier B.V. Ireland Ltd and the Japan Neuroscience Society.

Envolvimento da neurotransmissão glutamatérgica do núcleo leito da estria terminal (NLET) nas respostas autônomas ao estresse por restrição agudo em ratos

O núcleo leito da estria terminal (NLET) é uma estrutura límbica localizada no prosencéfalo rostral, no qual constitui uma importante região no circuito neural das respostas comportamentais e fisiológicas a estímulos aversivos. Estudos anteriores demonstraram o envolvimento do NLET nas respostas cardiovasculares desencadeados por estímulos aversivos. No entanto, os mecanismos neuroquímicos locais envolvidos nesse controle pelo NLET ainda são pouco compreendidos. O glutamato é um importante neurotransmissor excitatório no SNC, e evidências têm apontado que a neurotransmissão glutamatérgica é um importante mecanismo neuroquímico envolvido no controle das respostas fisiológicas durante o estresse em várias estruturas límbicas. Entretanto, um possível envolvimento da neurotransmissão glutamatérgica do NLET nas respostas cardiovasculares ao estresse nunca foi investigado. Assim, o objetivo do presente estudo foi estudar o envolvimento da neurotransmissão glutamatérgica no NLET nas respostas autônomas observadas durante o estresse de restrição agudo em ratos. Nós observamos que a microinjeção bilateral no NLET de LY235959 (antagonista seletivo do receptor glutamatérgico NMDA) reduziu a resposta taquicárdica desencadeada pelo estresse de restrição, porém não afetou as respostas pressora e de redução da temperatura cutânea da cauda. O tratamento bilateral do NLET com NBQX (antagonista seletivo de receptores glutamatérgicos não-NMDA) reduziu a resposta taquicárdica e a de redução da temperatura cutânea desencadeadas pelo estresse de restrição, porém sem interferir com a resposta pressora. Dessa forma, nossos dados sugerem que a neurotransmissão glutamatérgica do NLET tem uma influência facilitatória nas respostas taquicárdica e de vasoconstrição cutânea induzidas pelo estresse.