The tachycardia associated with the defense reaction involves activation of both GABAA and GABAB receptors in the nucleus tractus solitarii.
In urethane-anesthetized rats, the tachycardia associated with the defense reaction can be elicited by unilateral microinjections of the GABAA-antagonist, bicuculline methyliodide (BMI, 20 pmol), into the dorsomedial nucleus (DMN) of the hypothalamus. This effect is thought to be mediated via a pathway that activates GABAergic interneurons in the medullary nucleus tractus solitarii (NTS) which, in turn, inhibit vagal outflow to the heart. Ipsilateral intra-NTS microinjection of BMI (10 pmol) or the GABAB-antagonist, 2-OH-saclofen (400 pmol), attenuated the tachycardia elicited from the DMN. The tachycardia was also inhibited by intra-NTS administration of the NMDA-receptor channel blocker, MK-801 (30 pmol), or the non-NMDA antagonist, CNQX (400 pmol). These findings are interpreted to indicate that a) GABAergic control of heart rate at the level of the NTS is mediated by both GABAA and GABAB receptors, and b) descending input from the DMN to the NTS releases GABA via glutamate acting on ionotropic glutamate receptors located on GABAergic interneurons.
Kunos
G
G
Department of Pharmacology & Toxicology, Medical College of Virginia, Richmond 23298, U.S.A.
Varga
K
K
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000008:administration & dosage; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001640:Bicuculline / Q000008:administration & dosage / Q000031:analogs & derivatives; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects / Q000503:physiopathology; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D017552:Solitary Nucleus / Q000187:drug effects / Q000503:physiopathology*; D013315:Stress, Psychological / Q000503:physiopathology; D013610:Tachycardia / Q000209:etiology* / Q000503:physiopathology*
D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C017069:bicuculline methiodide; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001418:Baclofen; C057491:2-hydroxysaclofen; D001640:Bicuculline