Effect of Gamma-Aminobutyric Acid (GABA) and GABA Antagonist Drugs on ACTH ReleaseMakara G.B. · Stark E.
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest
Corticotrophin (ACTH) release has been studied in rats given intraventricular gamma-aminobutyric acid (GABA) infusions or injections of picrotoxin and bicuculline. As an index of ACTH release the corticosterone level of blood or plasma was determined. GABA (1 M/liter), infused at a rate of 1 µl/min into the 3rd ventricle, inhibited the rise in plasma corticosterone normally produced by surgical trauma. 60 min after surgical trauma the rats given GABA infusions had lower blood corticosterone levels than the control rats given infusions of 1 M/liter of proline, 1 M/liter of glycine, or 0.15 M/liter of sodium chloride. Picrotoxin, an antagonist of GABA, is a potent stimulus of ACTH release. In sub-convulsive intraperitoneal doses it produced a significant rise in plasma corticosterone in conscious rats with complete hypothalamic deafferentation. Under pentobarbital anesthesia 12.5 µg of picrotoxin injected into the 3rd ventricle produced a small but significant rise in plasma corticosterone in rats with hypothalamic deafferentation. After intraventricular injections of bicuculline methiodide a significant rise in plasma corticosterone occurred in rats with hypothalamic deafferentation; the ACTH releasing effect of 2.5 µg of bicuculline methiodide was strongly inhibited by a simultaneous infusion of 0.15 M/liter of GABA. On the basis of this pharmacological evidence, we suggest that GABA may be an inhibitory neurotransmitter of hypothalamic interneurons and/or afferent pathways involved in the regulation of ACTH release.
© 1974 S. Karger AG, Basel
Request reprints from: G.B. Makara, Institute of Experimental Medicine, Hungarian Academy of Sciences, P.O.B. 67, 1450 Budapest (Hungary)
Received: December 5, 1973
Revised MS accepted: June 4, 1974
Published online: March 20, 2008
Number of Print Pages : 13
Neuroendocrinology (International Journal for Basic and Clinical Studies on Neuroendocrine Relationships)
Vol. 16, No. 3-4, Year 1974 (Cover Date: 1974)
Journal Editor: Millar R.P. (Edinburgh)
ISSN: 0028–3835 (Print), eISSN: 1423–0194 (Online)
For additional information: http://www.karger.com/NEN