Localization of sites in periventricular forebrain mediating cardiovascular effects of gamma-aminobutyric acid agonists and antagonists in anesthetized cats.
Previous studies have shown that injection of gamma-aminobutyric acid (GABA) antagonists such as bicuculline methiodide (BMI) into the forebrain (i.e., lateral and third) ventricular system elicits neurally mediated increases in blood pressure and heart rate and inhibits baroreflex bradycardia in anesthetized cats. Similar administration of muscimol, a GABA agonist, blocks or reverses the effects of BMI but has no effect on blood pressure or heart rate in untreated animals. These findings suggest that GABAergic inhibition may tonically suppress a forebrain mechanism capable of modifying autonomic outflow to the cardiovascular system. In the present study, we used a technique designed to restrict the distribution of intraventricularly administered drugs to varying degrees in order to better localize the relevant sites of drug action. Our findings show that BMI increases heart rate and blood pressure and that muscimol counters these changes by acting at a site that is accessible from the intermediate (as opposed to the rostral or caudal) region of the third ventricle. In contrast, these agents influence baroreflex bradycardia by acting at more rostral periventricular sites. These findings are consistent with the notion that the GABAergic mechanisms involved in the cardiovascular effects resulting from intraventricular administration of BMI and muscimol are located in the periventricular hypothalamus.
D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D001931:Brain Mapping; D002415:Cats; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007031:Hypothalamus / Q000502:physiology; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000494:pharmacology; D009118:Muscimol / Q000008:administration & dosage*; D011963:Receptors, GABA-A / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D007608:Kainic Acid; D001640:Bicuculline