Skip to main content
SpringerLink
Log in

Effect of haloperidol on glutamete decarboxylase activity in discrete brain areas of the rat

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Using freeze-dried samples of rat brain, the effect of haloperidol on glutamate decarboxylase (GAD) activity without exogenously added pyridoxal-5′-phosphate (PLP) was studied in discrete brain nuclei and areas. Repeated injections of haloperidol produced significant changes in GAD activity in the dorsal part of the caudate nucleus, entopeduncular nucleus, pars reticulata of the substantia nigra, lateral hypothalamic area, and dorsomedial hypothalamic nucleus. A reduction of GAD activity after haloperidol was observed in the entopeduncular nucleus and pars reticulata of the substantia nigra. This finding demonstrates biochemically that haloperidol-induced extrapyramidal behavior may be involved in the reduction of GABAergic transmission in the entopeduncular nucleus and pars reticulata of the substantia nigra. A decrease in GAD activity in the lateral hypothalamic area indicates that interaction between GABAergic neurons as well as dopaminergic neurons may be involved in the haloperidol-induced behavioral changes. In addition, close interaction between GABAergic and dopaminergic systems in the dorsomedial hypothalamic nucleus and dorsal part to the caudate nucleus was demonstrated.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Albers RW, Brady RO (1959) The distribution of glutamate decarboxylase in the nervous system of the rhesus monkey. J Biol Chem 234:926–928

    Google Scholar 

  • Cools AR, Jansen HJ (1976) γ-Aminobutyric acid: The essential mediator of behavior triggered by neostriatally applied apomorphine and haloperidol. J Pharm Pharmacol 28:70–74

    Google Scholar 

  • Costa E, Fratta W, Hong JS, Moroni F, Yang HYT (1978) Interactions between enkephalinergic and other neuronal systems. In: Costa E, Trabucchi M (eds) Advances in biochemical psychopharmacology, vol. 18. Raven, New York, pp 217–226

    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 striato-pallidal, striato-entopeduncular and striatonigral GABAergic fibers. Brain Res 143:125–138

    Google Scholar 

  • Fonnum F, Grofova I, Rinvik E, Storm-Mathisen J, Walberg F (1974) Origin and distribution of glutamate decarboxylase in substantia nigra of the cat. Brain Res 71:77–92

    Google Scholar 

  • Gold BI, Roth RH (1979) Glutamate decarboxylase activity in striatal slices: Characterization of the increase following depolarization. J Neurochem 32:883–888

    Google Scholar 

  • Gundlach AL, Beart PM (1981) Differential effects of IV and IP muscimol on central dopamine metabolism. Psychopharmacology 74:71–73

    Google Scholar 

  • Itoh M, Uchimura H (1981) Regional differences in cofactor saturation of glutamate decarboxylase in discrete brain nuclei of the rat. Neurochem Res 6:1277–1283

    Google Scholar 

  • Kim JS, Hassler R (1975) Effects of acute haloperidol on the gammaaminobutyric acid system in rat striatum and substantia nigra. Brain Res 88:150–153

    Google Scholar 

  • König JFR, Klippel RA (1963) The rat brain. Williams & Wilkins, Baltimore

    Google Scholar 

  • Lloyd KG, Hornykiewicz O (1977) Effect of chronic neuroleptic or l-dopa administration on GABA levels in the rat substantia nigra. Life Sci 21:1489–1496

    Google Scholar 

  • Mao CC, Cheney DL, Marco E, Revuelta A, Costa E (1977) Turnover times of gamma-aminobutyric acid and acetylcholine in nucleus caudatus, nucleus accumbens, globus pallidus and substantia nigra: Effect of repeated administration of haloperidol. Brain Res 132:375–379

    Google Scholar 

  • Marco E, Mao CC, Revuelta A, Peralta E, Costa E (1978) Turnover rates of γ-aminobutyric acid in substantia nigra, n. caudatus, globus pallidus and n. accumbens of rats injected with cataleptogenic and noncataleptogenic antipsychotics. Neuropharmacology 17:589–596

    Google Scholar 

  • McGeer PL, McGeer EG (1975) Evidence for glutamic acid decarboxylase-containing interneurons in the neostriatum. Brain Res 91:331–335

    Google Scholar 

  • Miller LP, Martin DL, Mazumder A, Walters JR (1978) Studies on the regulation of GABA synthesis: Substrate-promoted dissociation of pyridoxal-5′-phosphate from GAD. J Neurochem 30:361–369

    Google Scholar 

  • Miller LP, Walters JR, Martin DL (1977) Post-mortem changes implicate adenine nucleotides and pyridoxal-5′-phosphate in regulation of brain glutamate decarboxylase. Nature 266:847–848

    Google Scholar 

  • Morelli M, Porceddu ML, Imperato A, DiChiara G (1981) Role of substantia nigra pars reticulata neurons in the expression of neuroleptic-induced catalepsy. Brain Res 217:375–379

    Google Scholar 

  • Moskal JR, Basu S (1975) The measurement of glutamate decarboxylase activity in brain tissue by a simple microradiometric method. Anal Biochem 65:449–457

    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 

  • Nisticó G, DiGiorgio RM, DeLuca G, Macaione S (1979) Effects of ethanolamine-O-sulphate and γ-acetylenic-GABA on GABA content, GAD and GABA-T in various areas of chick brain after intraventricular microinjection. J Neurochem 33:343–346

    Google Scholar 

  • Panksepp J (1981) Hypothalamic integration of behavior. In: Morgane PJ, Panksepp J (eds) Behavioral studies of hypothalamus. Marcel Dekker, New York Basel, pp 289–431

    Google Scholar 

  • Roberts E, Kuriyama K (1968) Biochemical-physiological correlations in studies of γ-aminobutyric system. Brain Res 8:1–35

    Google Scholar 

  • Scheel-Krüger J, Magelund G (1981) GABA in the entopeduncular nucleus and subthalamic nucleus participates in mediating dopaminergic striatal output functions. Life Sci 29:1555–1562

    Google Scholar 

  • Starr MS (1979) GABA-mediated potentiation of amine release from nigrostriatal dopamine neurons in vitro. Eur J Pharmacol 53:215–226

    Google Scholar 

  • Stoof JC, Den Breejen EJS, Mulder AH (1979) GABA modulates the release of dopamine and acetylcholine from rat caudate nucleus slices. Eur J Pharmacol 57:35–42

    Google Scholar 

  • Tapia R, Sandoval ME, Contreras P (1975) Evidence for a role of glutamate decarboxylase activity as a regulatory mechanism of cerebral excitability. J Neurochem 24:1283–1285

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuropsychiatry, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, 812, Fukuoka, Japan

    Masatoshi Itoh

Authors
  1. Masatoshi Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Itoh, M. Effect of haloperidol on glutamete decarboxylase activity in discrete brain areas of the rat. Psychopharmacology 79, 169–172 (1983). https://doi.org/10.1007/BF00427805

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00427805

Key words

Search

Navigation