Research Report Effect of glutamate stimulation of the cuneiform nucleus on cardiovascular regulation in anesthetized rats: Role of the pontine Kolliker–Fuse nucleus Mohammad Naser Shafei a , Ali Nasimi b, ⁎ a Department of Physiology, Mashhad University of Medical Sciences, Mashhad, Iran b Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran ARTICLE INFO ABSTRACT Article history: Accepted 14 February 2011 Available online 22 February 2011 Cuneiform nucleus (CnF) is a reticular nucleus of the midbrain involved in cardiovascular function and stress. There is no report on the cardiovascular effects of the glutamatergic system in the CnF. In the present study, we investigated the cardiovascular effects of glutamate and its NMDA and AMPA/kainate receptors in the CnF. In addition, the possible mediation of Kolliker–Fuse (KF) nucleus in the cardiovascular effects of the CnF was explored. L-glutamate, AP5 (an NMDA receptor antagonist), and CNQX (an AMPA/kainate receptor antagonist) (50–100 nl) were microinjected into the CnF of anesthetized rats. Also, the KF was blocked by cobalt chloride (CoCl 2 ) then L-glutamate was microinjected into the CnF. The maximum changes of blood pressure and heart rate were compared with the pre- injection (paired t-test) and control (independent t-test) values. Microinjection of glutamate (25 nmol/100 nl) into the CnF produced either a short pressor and bradycardic or a long pressor and tachycardic responses. Microinjection of AP5 or CNQX alone did not affect the basal arterial pressure and heart rate. However, co-injection of glutamate with AP5 strongly attenuated the short and moderately attenuated the long cardiovascular responses elicited by glutamate. Co-injection of glutamate with CNQX did not attenuate the short and weakly attenuated the long cardiovascular responses elicited by glutamate. These data suggest that the responses are mediated mainly through NMDA receptors. Blockade of the KF nucleus strongly attenuated the short response and weakly attenuated the long response to glutamate microinjection, suggesting that the cardiovascular effects of glutamate in the CnF, especially the short responses, were mediated by the KF nucleus. © 2011 Elsevier B.V. All rights reserved. Keywords: Cuneiform nucleus Kolliker–Fuse nucleus Glutamate Arterial pressure Heart rate NMDA 1. Introduction The cuneiform nucleus (CnF) is a mesencephalic nucleus involved in cardiovascular responses to threatening or painful stimuli (Korte et al., 1992; Verberne, 1995; Lam et al., 1996), modulation of pain (Haghparast et al., 2007), and motor activity (Allen et al., 1996). Neuroanatomical and histochemical studies have shown that CnF is connected with regions involved in cardiovascular modulation, such as the periaqueductal gray matter (PAG), the parabrachial/Kolliker–Fuse complex, the BRAIN RESEARCH 1385 (2011) 135 – 143 ⁎ Corresponding author. Fax: +98 311 6688597. E-mail address: nasimi@med.mui.ac.ir (A. Nasimi). 0006-8993/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2011.02.046 available at www.sciencedirect.com www.elsevier.com/locate/brainres