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Characterization of extracellular GABA in the substantia nigra reticulata by means of brain microdialysis

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Summary

Brain microdialysis was used to characterize extracellular gamma-aminobutyric acid (GABA) in the substantia nigra reticulata (SNR) of freely moving rats. The extracellular GABA in the SNR was characterized using acutely implanted probes (4–8 h after surgery; day 1) and chronically implanted probes (24 h after surgery; day 2).

3-Mercaptopropionic acid, a glutamic acid decarboxylase inhibitor, was used to identify GABA. This drug induced an immediate decrease in the extracellular GABA levels to 40% of basal values, suggesting that the detected GABA is, at least in part, newly synthesized.

The basal levels of extracellular GABA measured either on day 1 or day 2 were not affected by infusion of micromolar amounts of tetrodotoxin. Therefore, a direct coupling between GABA dialysate concentrations and nerve-impulse flow does not seem to exist. Infusion of the GABA uptake inhibitor nipecotic acid (0.5 mmol/l) resulted in a 4-fold increase in the dialysate levels of GABA lasting at least for 3 h on both days. K+ stimulation (60 mmol/l) increased extracellular GABA levels in the SNR to 450% of basal values. This effect again did not differ significantly on day 1 and day 2.

The origin of the extracellular GABA in the SNR, as recorded by microdialysis under the two experimental conditions, is discussed.

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References

  • Arbilla S, Kamal L, Langer SZ (1979) Presynaptic GABA autoreceptors on GABA-ergic nerve endings of the rat substantia nigra. Eur J Pharmacol 57:211–217

    Google Scholar 

  • Bernath S, Keller RW Jr, Zigmond MJ (1989) Release of endogenous GABA can occur through Ca2+-dependent and Ca2+-independent processes. Neurochem Int 14:439–445

    Google Scholar 

  • Bourdelais A, Kalivas PW (1990) Amphetamine lowers extracellular GABA concentration in the ventral pallidum. Brain Res 516:132–136

    Google Scholar 

  • Brownstein MJ, Mroz EA, Tappaz ML, Leeman SE (1977) On the origin of substance P and glutamic acid decarboxylase (GAD) in the substantia nigra. Brain Res 135:315–323

    Google Scholar 

  • Damsma G, De Boer P, Westerink BHC, Fibiger HC (1990) Dopaminergic regulation of striatal cholinergic interneurons: an in vivo microdialysis study. Naunyn-Schmiedeberg's Arch Pharmacol 342: 523–527

    Google Scholar 

  • De Boer P, Damsma G, Fibiger HC, Timmerman W, De Vries JB, Westerink BHC (1990) Dopaminergic-cholinergic interactions in the striatum: the critical significance of calcium concentrations in brain microdialysis. Naunyn-Schmiedeberg's Arch Pharmacol 342:528–534

    Google Scholar 

  • DeLong MR, Georgopoulos AP, Crutcher MD, Mitchell SJ, Richardson RT, Alexander GE (1984) Functional organization of the basal ganglia: contributions of single-cell recording studies. In: Evered D, O'Connor M (eds) Functions of the basal ganglia. Pitman, London, pp 64–82

    Google Scholar 

  • Drew KL, O'Connor WT, Kehr J, Ungerstedt U (1989) Characterization of gamma-aminobutyric acid and dopamine overflow following acute implantation of a microdialysis probe. Life Sci 45:1307–1317

    Google Scholar 

  • Drew KL, O'Connor WT, Kehr J, Ungerstedt U (1990) Regional specific effects of clozapine and haloperidol on GABA and dopamine release in rat basal ganglia. Eur J Pharmacol 187:385–397

    Google Scholar 

  • Drew KL, Ungerstedt U (1991) D2 receptor stimulation presynaptically inhibits calcium stimulated release of y-aminobutyric acid from rat dorsolateral striatum. In: Rollema H, Westerink BHC, Drijfhout WJ (eds) Monitoring molecules in neuroscience. Univ of Groningen, Groningen, pp 102–104

    Google Scholar 

  • Fonnum F, Gottesfeld Z, Grofova I (1978) Distribution of glutamate decarboxylase, choline acetyltransferase and aromatic amino acid decarboxylase in the basal ganglia of normal and operated rats. Evidence for striatopallidal, striatoentopeduncular and striatonigral GABAergic fibres. Brain Res 143:125–138

    Google Scholar 

  • Giralt MT, Bonanno G, Raiteri M (1990) GABA terminal autoreceptors in pars compacta and in pars reticulata of the rat substantia nigra are both GABAB. Eur J Pharmacol 175:137–144

    Google Scholar 

  • Girault JA, Spampinato U, Savaki HE, Glowinski J, Besson J (1986) In vivo release of [3H]γ-aminobutyric acid in the rat neostriatum —I. Characterization and topographical heterogeneity of the effects of dopaminergic and cholinergic agents. Neurosci 19:1101–1108

    Google Scholar 

  • Jessell TM, Emson PC, Paxinos G, Cuello CA (1978) Topographic projections of substance P and GABA pathways in the striato- and pallido-nigral systems: a biochemical and immunohistochemical study. Brain Res 152:487–498

    Google Scholar 

  • Kalivas PW, Bourdelais AJ (1991) Dialysis of GABA in the ventral pallidum: modulation by dopamine. In: Rollema H, Westerink BHC, Drijfhout WJ (eds) Monitoring molecules in neuroscience. Univ of Groningen, Groningen, pp 90–92

    Google Scholar 

  • Kehr J, Ungerstedt U (1988) Fast HPLC estimation of γ-aminobutyric acid in microdialysis perfusates: Effect of nipecotic and 3-mercaptopropionic acids. J Neurochem 51:1308–1310

    Google Scholar 

  • Moghaddam B, Bunney BS (1989) Ionic composition of microdialysis perfusing solution alters the pharmacological responsiveness and basal outflow of striatal dopamine. J Neurochem 53:652–654

    Google Scholar 

  • Nagy JI, Carter DA, Fibiger HC (1978) Anterior striatal projections to the globus pallidus, entopeduncular nucleus and substantia nigra in the rat: the GABA connection. Brain Res 158:15–29

    Google Scholar 

  • Oertel WH, Mugnaini E (1984) Immunocytochemical studies of GABAergic neurons in rat basal ganglia and their relations to other neuronal systems. Neurosci Lett 47:233–238

    Google Scholar 

  • Oertel WH, Schmechel DE, Brownstein MJ, Vappaz ML, Ransom DH, Kopin IJ (1981) Decrease of glutamate decarboxylase (GAD)-immunoreactive nerve terminals in the substantia nigra after kainic acid lesion of the striatum. J Histochem Cytochem 29:977–980

    Google Scholar 

  • Osborne PG, O'Connor WT, Drew KL, Ungerstedt U (1990) An in vivo microdialysis characterization of extracellular dopamine and GABA in dorsolateral striatum of awake freely moving and halothane anaesthetised rats. J Neurosci Methods 34:99–105

    Google Scholar 

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

    Google Scholar 

  • Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates, 1st edn. Academic Press, London

    Google Scholar 

  • Reubi JC, Iversen LL, Jessell TM (1977) Dopamine selectively increases 3 H-GABA release from slices of rat substantia nigra in vitro. Nature 268:652–654

    Google Scholar 

  • Roberts E (1979) New direction in GABA research I: Immunocytochemical studies of GABA neurons. In: Krogsgaard-Larsen P, ScheelKruger J, Kofod H (eds) GABA neurotransmitters. Pharmacochemical, biochemical and pharmacological aspects. Munksgaard, Copenhagen, pp 28–45

    Google Scholar 

  • Santiago M, Westerink BHC (1990) Characterization of the in vivo release of dopamine as recorded by different types of intracerebral microdialysis probes. Naunyn-Schmiedeberg's Arch Pharmacol 342:407–414

    Google Scholar 

  • Van der Heyden JAM, Venema K, Korf J (1979) In vivo release of endogenous GABA from rat substantia nigra measured by a novel method. J Neurochem 32:469–476

    Google Scholar 

  • Van der Heyden JAM, Venema K, Korf J (1980) In vivo release of endogenous γ-aminobutyric acid from rat striatum: Effects of muscimol, oxotremorine, and morphine. J Neurochem 34:1648–1653

    Google Scholar 

  • Waldmeier P, Wicki P, Feldtrauer JJ, Baumann PA (1988) Potential involvement of a baclofen-sensitive autoreceptor in the modulation of the release of endogenous GABA from the rat brain slices in vitro. Naunyn-Schmiedeberg's Arch Pharmacol 337:289–295

    Google Scholar 

  • Waldmeier PC, Wicki P, Feldtrauer JJ, Baumann PA (1989) Release of endogenous GABA from the substantia nigra is not controlled by GABA autoreceptors. Naunyn-Schmiedeberg's Arch Pharmacol 340:372–378

    Google Scholar 

  • Westerink BHC, Hofsteede HM, Damsma G, De Vries JB (1988) The significance of extracellular calcium for the release of dopamine, acetylcholine and amino acids in conscious rats, evaluated by brain microdialysis. Naunyn-Schmiedeberg's Arch Pharmacol 337: 373–378

    Google Scholar 

  • Westerink BHC, 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 

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Timmerman, W., Zwaveling, J. & Westerink, B.H.C. Characterization of extracellular GABA in the substantia nigra reticulata by means of brain microdialysis. Naunyn-Schmiedeberg's Arch Pharmacol 345, 661–665 (1992). https://doi.org/10.1007/BF00164580

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