Injection of muscimol into posterior hypothalamus blocks stress-induced tachycardia.
We have previously shown that the physiological and behavioral manifestations of emotional stress are produced when drugs impairing gamma-aminobutyric acid (GABA)-mediated synaptic inhibition are injected into the posterior hypothalamic nucleus in rats [Wible, J.H., Jr., F.C. Luft, and J.A. DiMicco. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R680-R687, 1988]. The purpose of this study was to assess further the potential role of GABA receptors in this region in the response to stress using muscimol, a GABAA receptor agonist. In six chronically instrumented conscious rats, air stress after vehicle treatment evoked marked and sustained tachycardia (+130 +/- 14 beats/min at +10 min) accompanied by a less dramatic increase in arterial pressure (+14 +/- 3 mmHg). Microinjection of muscimol (10 ng; 88 pmol) at the same posterior hypothalamic site in which GABA blockade causes cardiovascular changes similar to those seen in stress produced a modest depression of cardiovascular function in unstressed animals (-28 +/- 5 beats/min and -6 +/- 3 mmHg). However, similar treatment with muscimol virtually abolished the stress-induced tachycardia in the same rats (+9 +/- 8 beats/min), while having no significant effect on baroreflex-evoked increases in heart rate caused by intravenous infusion of sodium nitroprusside (4 micrograms). These findings support a role for activation of neurons in the posterior nucleus of the hypothalamus in the generation of stress-induced cardiovascular changes and for control of this mechanism by local GABA receptors.
Lisa
M
M
Department of Pharmacology, Indiana University School of Medicine, Indianapolis 46223.
Marmo
E
E
Wible
J H
JH
DiMicco
J A
JA
D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D007031:Hypothalamus / Q000502:physiology*; D007034:Hypothalamus, Posterior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D009118:Muscimol; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline