Skip to main content
Log in

Release of endogenous GABA in the posterior hypothalamus of the conscious rat; effects of drugs and experimentally induced blood pressure changes

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Push-pull superfusion was used to investigate the release of endogenous GABA in the posterior hypothalamus of the conscious, freely moving rat at basal conditions and in response to centrally applied drugs or to peripherally induced blood pressure changes.

After an initial, exponential decline, the release rate of GABA remained fairly constant for many hours. Fluctuations in the release rate of GABA point to the existence of an ultradian rhythm with an approximate frequency of 1 cycle/65 min. Hypothalamic superfusion with a potassium-rich (50 or 90 mmol/1) artificial cerebrospinal fluid led to a concentration-dependent increase in the GABA release. The release of GABA was also enhanced by veratridine (1 or 10 μmol/1) in a concentration-dependent way. Hypothalamic superfusion with the neutrotoxin tetrodotoxin (1 gmmol/1) led to a long-lasting decrease in the GABA release. The rise in blood pressure (45 mmHg) elicited by an intravenous infusion of noradrenaline was associated with an increased release rate of GABA in the hypothalamus. Hypotension produced by nitroprusside (25 mmHg) led to a counteracting decrease in hypothalamic GABA outflow.

The findings suggest that approximately 4510 of the basal outflow of GABA found in the superfusate are released from GABA-ergic neurons of the posterior hypothalamus. The release rate of GABA fluctuates according to an ultradian rhythm. The modified release of GABA in response to experimentally induced blood pressure changes suggests that, in the posterior hypothalamus of the conscious rat, GABAergic neurons are involved in cardiovascular control and possess a hypotensive function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Anderson JJ, DiMicco JA (1990) Effect of local inhibition of γ-aminobutyric acid uptake in the dorsomedial hypothalamus on extracellular levels of γ-aminobutyric acid and on stress-induced tachycardia: a study using microdialysis. J Pharmacol Exp Ther 255:1399–1407

    Google Scholar 

  • Bourdelais AJ, Kalivas PW (1992) Modulation of γ-aminobutyric acid in the ventral pallidum using in vivo microdialysis. J Neurochem 58:2311–2320

    Google Scholar 

  • Dietl H, Philippu A (1979) In vivo release of endogenous GABA in the cat hypothalamus. Naunyn-Schmiedeberg's Arch Pharmacol 308:143–147

    Google Scholar 

  • Dietl H, Prast H, Philippu A (1993) Pulsatile release of catecholamines in the hypothalamus of conscious rats. Naunyn-Schmiedeberg's Arch Pharmacol 347:28–33

    Google Scholar 

  • Drew KL, Ungerstedt U (1991) Pergolide presynaptically inhibits calcium-stimulated release of γ-aminobutyric acid. J Neurochem 57:1927–1930

    Google Scholar 

  • Herbison AE, Heavens RP, Dyer RG (1990) Endogenous release of γ-aminobutyric acid from the medial preoptic area measured by microdialysis in the anaesthetised rat. J Neurochem 55:1617–1623

    Google Scholar 

  • Lanzinger I, Kobilanski C, Philippu A (1989) Pattern of catecholamine release in the nucleus tractus solitarii of the cat. Naunyn-Schmiedeberg's Arch Pharmacol 339:298–301

    Google Scholar 

  • Meyer DK, Oertel WH, Brownstein MJ (1980) Deafferentation studies on the glutamic acid decarboxylase content of the supraoptic nucleus of the rat. Brain Res 200:165–168

    Google Scholar 

  • Minchin MCW, Iversen LL (1974) Release of 3H-γ-aminobutyric acid from glial cells in rat dorsal root ganglia. J Neurochem 23:533–540

    Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, Sydney

    Google Scholar 

  • Paulsen RE, Fonnum F (1989) Role of glial cells for the basal and Ca2+-dependent K+-evoked release of transmitter amino acids investigated by microdialysis. J Neurochem 52:1823–1829

    Google Scholar 

  • Philippu A (1984) Use of push-pull cannulae to determine the release of endogenous neutrotransmitters in distinct brain areas of anaesthetized and freely moving animals. In: Marsden CA (ed) Measurement of neurotransmitters release in vivo. John Wiley, Chichester, pp 3–73

    Google Scholar 

  • Philippu A (1988) Regulation of blood pressure by central neurotransmitters and neuropeptides. Rev Physiol Biochem Pharmacol 111:1–115

    Google Scholar 

  • Philippu A, Died H, Sinha JN (1979) In vivo release of endogenous catecholamines in the hypothalamus. Naunyn-Schmiedeberg's Arch Pharmacol 308:137–142

    Google Scholar 

  • Philippu A, Hanesch U, Hagen R, Robinson RL (1982) Release of endogenous histamine in the hypothalamus of anaesthetized cats and conscious, freely moving rabbits. Naunyn-Schmiedeberg's Arch Pharmacol 321:282–286

    Google Scholar 

  • Prast H, Saxer A, Philippu A (1988) Pattern of in vivo release of endogenous histamine in the mamillary body and the amygdala. Naunyn-Schmiedeberg's Arch Pharmacol 337:53–57

    Google Scholar 

  • Prast H, Died H, Philippu A (1992) Pulsatile release of histamine in the hypothalamus of conscious rats. J Anton Nerv Syst 39:105–110

    Google Scholar 

  • Singewald, N, Pfitscher A, Philippu A (1992) Effects of gamma-vinyl GABA (vigabatrin) on blood pressure and body weight of hypertensive and normotensive rats. Naunyn-Schmiedeberg's Arch Pharmacol 345:181–186

    Google Scholar 

  • Somjen CG, Allen BW, Balestrino M, Aitken P (1987) Pathophysiology of pH and Ca2+ in bloodstream and brain. Can J Physiol Pharmacol 65:1078–1085

    Google Scholar 

  • Tappaz ML, Brownstein MJ, Kopin IJ (1977) Glutamate decarboxylase (GAD) and γ-aminobutyric acid (GABA) in discrete nuclei of hypothalamus and substantia nigra. Brain Res 125:109–121

    Google Scholar 

  • Tappaz ML, Wassef M, Oertel WH, Paut L, Pujol JF (1983) Light- and electron-microscopic immunocytochemistry of glutamic acid decarboxylase (GAD) in the basal hypothalamus: morpholgical evidence for neuroendocrine γ-aminobutyrate (GABA). Neuroscience 9:271–287

    Google Scholar 

  • Tossman U, Jonsson G, Ungerstedt U (1986) Regional distribution and extracellular levels of amino acids in rat central nervous system. Acta Physiol Scand 127:533–545

    Google Scholar 

  • Westerink BHC and de Vries JB (1989) On the origin of extracellular GABA collected by brain microdialysis and assayed by a simplified on-line method. Naunyn-Schmiedeberg's Arch Pharmacol 339: 603–607

    Google Scholar 

  • Wible JH, Luft FC, DiMicco JA (1988) Hypothalamic GABA suppresses sympathetic outflow to the cardiovascular system. Am J Physiol 254:R680-R687

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung

Correspondence to N. Singewald at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

Singewald, N., Guo, L. & Philippu, A. Release of endogenous GABA in the posterior hypothalamus of the conscious rat; effects of drugs and experimentally induced blood pressure changes. Naunyn-Schmiedeberg's Arch Pharmacol 347, 402–406 (1993). https://doi.org/10.1007/BF00165390

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00165390

Key words

Navigation