Summary
Rats lightly anesthetized with halothane were treated with graded intraperitoneal doses of gamma-hydroxybutyric acid (GHBA), a GABA analogue. The drug induced a dose dependent decrease in minute ventilation, mainly due to reduced respiratory frequency. A reduced pH in arterial blood was recorded. GHBA also blunted or abolished the respiratory response to CO2 exposure in a dose-related way. Picrotoxin (0.25, 0.5 or 1.0 mg/kg intravenously), a presumed GABA antagonist did not significantly change the respiratory pattern when given alone but clearly antagonized the GHBA-induced respiratory depression. It is concluded that GABA-ergic mechanisms are involved in central respiratory control.
This is a preview of subscription content, log in via an institution to check access.
References
Armijo, J. A., Flórez, J. The influence of increased brain 5-hydroxytryptamine upon the respiratory activity of cats. Neuropharmacology13, 977–986 (1974).
Bessman, S. P., Fishbein, W. N. Gamma-Hydroxybutyrate, a normal brain metabolite. Nature200, 1207–1209 (1973).
Biswas, B., Carlsson, A. The effect of intracerebroventricularly administered GABA on brain monoamine metabolism. Naunyn-Schmiedeberg's Arch. Pharmacol.299, 41–46 (1977).
Bolme, P., Fuxe, K. Pharmacological studies on a possible role of central noradrenaline neurons in respiratory control. J. Pharm. Pharmacol.25, 351–352 (1973).
Carlsson, A., Biswas, B., Lindqvist, M. Influence of GABA and GABA-like drugs on monoaminergic mechanisms. In: Advances in Biochemical Psychopharmacology, Vol. 16 (Costa, E., Gessa, G. L., eds.), pp. 471 to 475. New York: Raven Press. 1977.
Elliott, K. A. C., Hobbiger, F. Gamma-aminobutyric acid: circulatory and respiratory effects in different species; re-investigation of the antistrychnine action in mice. J. Physiol. (Lond.)146, 70–84 (1959).
Holzer, P., Hagmüller, K. Transient apnoea after systemic injection of GABA in the rat. Naunyn-Schmiedeberg's Arch. Pharmacol.308, 55–60 (1979).
Krnjevic, K. Chemical nature of synaptic transmission in vertebrates. Physiol. Rev.54, 418–540 (1974).
Lundberg, D., Breese, G. R., Mueller, R. Dopaminergic interaction with the respiratory control system in the rat. Eur. J. Pharmacol.54, 153 to 159 (1979).
Mueller, R., Lundberg, D., Breese, G. R. Evidence that respiratory depression by serotonin agonists may be exerted in the central nervous system. Pharmac. Biochem. Behav.13, 247–255 (1980).
Roth, R. H., Giarman, N. J. Conversionin vivo ofγ-aminobutyric toγ-hydroxybutyric acid in the rat. Biochem. Pharmacol.18, 247–250 (1968).
Roth, R. R., Walters, J. R., Aghajanian, G. K. Frontiers in catecholamine research, pp. 567–574. New York: Pergamon Press. 1973.
Schläfke, M. E., Soe, W. R., Loeschcke, H. H. Ventilatory response to alterations of H+-ion concentration in small areas of the ventral medullary surface. Resp. Physiol.10, 198–212 (1970).
Ticku, M. K., Van Ness, P. C., Haycock, J. W., Levy, W. B., Olsen, R. W. Dihydropicrotoxinin binding sites in rat brain: comparison to GABA receptors. Brain Res.150, 642–647 (1978).
Usherwood, P. N., Grundfest, H. Inhibitory postsynaptic potentials in grasshopper muscle. Science143, 817–818 (1964).
Yebenes, J. G., Carlsson, A., Gomez, M. A. M. The effect of CO2 on monoamine metabolism in rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol.301, 11–15 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hedner, J., Jonason, J. & Lundberg, D. Respiratory effects of gamma-hydroxybutyric acid in anesthetized rats. J. Neural Transmission 49, 179–186 (1980). https://doi.org/10.1007/BF01245223
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01245223