title: Involvement of dorsal hippocampus glutamatergic and nitrergic neurotransmission in autonomic responses evoked by acute restraint stress in rats.
abstract: The dorsal hippocampus (DH) is a structure of the limbic system that is involved in emotional, learning and memory processes. There is evidence indicating that the DH modulates cardiovascular correlates of behavioral responses to stressful stimuli. Acute restraint stress (RS) is an unavoidable stress situation that evokes marked and sustained autonomic changes, which are characterized by elevated blood pressure (BP), intense heart rate (HR) increase and a decrease in cutaneous temperature. In the present study, we investigated the involvement of an N-methyl-D-aspartate (NMDA) glutamate receptor/nitric oxide (NO) pathway of the DH in the modulation of autonomic (arterial BP, HR and tail skin temperature) responses evoked by RS in rats. Bilateral microinjection of the NMDA receptor antagonist AP-7 (10 nmol/500 nL) into the DH attenuated RS-evoked autonomic responses. Moreover, RS evoked an increase in the content of NO₂/NO₃ in the DH, which are products of the spontaneous oxidation of NO under physiological conditions that can provide an indirect measurement of NO production. Bilateral microinjection of N-propyl-L-arginine (0.1 nmol/500 nL; N-propyl, a neuronal NO synthase (nNOS) inhibitor) or carboxy-PTIO (2 nmol/500 nL; c-PTIO, an NO scavenger) into the DH also attenuated autonomic responses evoked by RS. Therefore, our findings suggest that a glutamatergic system present in the DH is involved in the autonomic modulation during RS, acting via NMDA receptors and nNOS activation. Furthermore, the present results suggest that NMDA receptor/nNO activation has a facilitatory influence on RS-evoked autonomic responses.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
authors.forename: T B
authors.initials: TB
authors.lastname: Moraes-Neto
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: A A
authors.initials: AA
authors.lastname: Scopinho
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Biojone
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: F M A
authors.initials: FM
authors.lastname: Corrêa
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil. Electronic address: leoresstel@yahoo.com.br.
authors.forename: L B M
authors.initials: LB
authors.lastname: Resstel
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012149:Restraint, Physical; D015398:Signal Transduction / Q000187:drug effects; D012881:Skin Temperature / Q000187:drug effects; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology*; D013623:Tail
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D009566:Nitrates; D009573:Nitrites; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D015763:2-Amino-5-phosphonovalerate; D052248:Nitric Oxide Synthase Type I; C031231:2-amino-7-phosphonoheptanoic acid
keywords: 2-amino-7-phosphonoheptanoic acid; ACSF; ANOVA; AP-7; BNST; BP; BSA; DH; HR; LSA; MAP; MPFC; N(ω)-propyl-l-arginine; N-methyl-d-aspartate; N-propyl; NADPH; NMDA; NO; RS; SEM; analysis of variance; artificial cerebrospinal fluid; bed nucleus of stria terminalis; blood pressure; bovine serum albumin; c-PTIO; carboxy-PTIO(S)-3-carboxy-4-hydroxyphenylglicine; dorsal hippocampus; glutamate; heart rate; hippocampus; l-glu; lateral septal area; mean arterial pressure; medial prefrontal cortex; nNOS; neuronal nitric oxide synthase; nitric oxide; reduced form of nicotinamide adenine dinucleotide phosphate; restraint stress; standard error of mean