title: Sympathoexcitation and pressor responses induced by ethanol in the central nucleus of amygdala involves activation of NMDA receptors in rats.
abstract: The central nervous system plays an important role in regulating sympathetic outflow and arterial pressure in response to ethanol exposure. However, the underlying neural mechanisms have not been fully understood. In the present study, we tested the hypothesis that injection of ethanol in the central nucleus of the amygdala (CeA) increases sympathetic outflow, which may require the activation of local ionotropic excitatory amino acid receptors. In anesthetized rats, CeA injection of ethanol (0, 0.17, and 1.7 μmol) increased splanchnic sympathetic nerve activity (SSNA), lumbar sympathetic nerve activity (LSNA), and mean arterial pressure (MAP) in a dose-dependent manner. A cocktail containing ethanol (1.7 μmol) and kynurenate (KYN), an ionotropic excitatory amino acid receptor blocker, showed significantly blunted sympathoexcitatory and pressor responses compared with those elicited by CeA-injected ethanol alone (P < 0.01). A cocktail containing ethanol and d-2-amino-5-phosphonovalerate, an N-methyl-d-aspartate (NMDA) receptor antagonist, elicited attenuated sympathoexcitatory and pressor responses that were significantly less than ethanol alone (P < 0.01). In addition, CeA injection of acetate (0.20 μmol, n = 7), an ethanol metabolite, consistently elicited sympathoexcitatory and pressor responses, which were effectively blocked by d-2-amino-5-phosphonovalerate (n = 9, P < 0.05). Inhibition of neuronal activity of the rostral ventrolateral medulla (RVLM) with KYN significantly (P < 0.01) attenuated sympathoexcitatory responses elicited by CeA-injected ethanol. Double labeling of immune fluorescence showed NMDA NR1 receptor expression in CeA neurons projecting to the RVLM. We conclude that ethanol and acetate increase sympathetic outflow and arterial pressure, which may involve the activation of NMDA receptors in CeA neurons projecting to the RVLM.
authors.affiliation: Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; and.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Chapp
authors.affiliation: Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; and Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors.forename: Le
authors.initials: L
authors.lastname: Gui
authors.affiliation: Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; and.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Huber
authors.affiliation: Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; and.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Larson
authors.affiliation: Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; and.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Carter
authors.affiliation: Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; and qinghuic@mtu.edu.
authors.forename: Qing-Hui
authors.initials: QH
authors.lastname: Chen
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000200:Action Potentials; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013153:Splanchnic Nerves / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid
keywords: N-methyl-d-aspartate; acetate; amygdala; ethanol; glutamate receptors; sympathetic nerve activity