4.5 Article

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

Journal

EUROPEAN NEUROPSYCHOPHARMACOLOGY
Volume 23, Issue 11, Pages 1611-1622

Publisher

ELSEVIER
DOI: 10.1016/j.euroneuro.2012.11.002

Keywords

Anxiety; Cardiovascular; Elevated plus maze test; HPA axis; NMDA glutamate receptors; Non-NMDA glutamate receptors; PVN; Stress

Funding

  1. Foundation to Support Research of the State of Sao Paulo [FAPESP proc. 2009/05308-8, proc. 2010/09462-9, proc. 2010/16192-8]
  2. Coordination of Improvement of Higher Education Personnel [CAPES proc. PNPD0176087]
  3. National Counsel of Technological and Scientific Development [CNPq 505394/2003-0, 305996/2008-8]
  4. Foundation to Support Education, Research and Care at the Clinics Hospital, School of Medicine of Ribeirao Preto, University of Sao Paulo (FAEPA)
  5. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [10/16192-8] Funding Source: FAPESP

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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. (C) 2012 Elsevier B.V. and ECNR All rights reserved.

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