Ethanol inhibition of stress-related tachycardia involves medullary NMDA receptors.
In rats, neurons in the perifornical area of the hypothalamus send descending projections to the commissural part of the nucleus tractus solitarii as demonstrated by an anterograde tracer study. In urethane-anaesthetised rats, stimulation of neurons in the perifornical area by microinjection of bicuculline or 6-OH-saclofen causes tachycardia and inhibits baroreflex bradycardia. The effects elicited from the perifornical area are similar in magnitude to those elicited from the adjacent dorsomedial nucleus, also called the hypothalamic defense area. Microinjection into the nucleus tractus solitarii of the NMDA (N-methyl-D-aspartate) receptor antagonist, AP-7 (2-amino-7-phosphonoheptanoic acid), inhibits the tachycardic response to stimulation of the perifornical area. Injection of ethanol intravenously or into the nucleus tractus solitarii also inhibits this tachycardic response, but causes no further inhibition when combined with AP-7. We conclude that the perifornical area is part of the hypothalamic defense area, and it is under strong, tonic GABAergic inhibition mediated by both GABAA and GABAB receptors. Furthermore, descending input from the perifornical area to the nucleus tractus solitarii is via an NMDA synapse, and ethanol inhibits stress-related tachycardia by inhibiting these NMDA receptors in the nucleus tractus solitarii.
Varga
K
K
Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond 23298-0613, USA.
Lovas
G
G
Palkovits
M
M
Kunos
G
G
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D017552:Solitary Nucleus / Q000187:drug effects / Q000503:physiopathology; D013312:Stress, Physiological / Q000150:complications*; D013610:Tachycardia / Q000209:etiology / Q000517:prevention & control*
D018755:GABA Agonists; D018756:GABA Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D009118:Muscimol; D000431:Ethanol; D001418:Baclofen; C080629:saclofen; D001640:Bicuculline