GABAB receptors in the dorsomedial hypothalamus and heart rate in anesthetized rats.
Previous studies have shown that: (1) activation of neurons in the dorsomedial hypothalamus (DMH) of the rat by blockade of local GABAA receptors with bicuculline methiodide (BMI) elicits cardiovascular changes resembling those seen in experimental stress, including marked sympathetically-mediated tachycardia, and (2) inhibition of neurons in the same region by local microinjection of the GABAA receptor agonist muscimol can virtually abolish stress-induced tachycardia. This study examined the possibility that GABAB receptors exist in the neural circuitry of the DMH, and that stimulation of these receptors might suppress the cardiovascular response to local disinhibition with BMI. Microinjection of BMI 10 pmol into the DMH in urethane-anesthetized rats resulted in marked tachycardia with little or no effect on arterial pressure. Simultaneous injection of the GABAB receptor agonist baclofen at doses of 2.5, 5.0 and 10 pmol produced dose-related suppression of BMI induced tachycardia. Coinjection of the GABAB receptor antagonist 2-hydroxysaclofen 100 or 200 pmol had no significant effect on the heart rate response to BMI, but reversed the suppression elicited in the presence of baclofen. These findings indicate that (1) functional GABAB receptors exist in the DMH, and (2) stimulation of these receptors inhibits the tachycardia resulting from blockade of local GABAA receptors.
DiMicco
J A
JA
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, USA.
Monroe
A J
AJ
D000777:Anesthetics; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D007033:Hypothalamus, Middle / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects*
D000777:Anesthetics; D018755:GABA Agonists; D018756:GABA Antagonists; D018080:Receptors, GABA-B; C017069:bicuculline methiodide; D001418:Baclofen; C080629:saclofen; D001640:Bicuculline