Skip to main content
Log in

Effect of sodium valproate on motor function regulated by the activation of GABA receptors

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

Abstract

Sodium valproate is an anticonvulsant which elevates GABA levels in the brain. GABA interacts with dopamine functionally in certain areas of the brain involved in motor behavior such as the nucleus accumbens and the substantia nigra. In order to determine whether GABA can play a functional role in the pharmacological effects of valproate, both valproate and GABA were injected directly into these two brain areas and the effects of these compounds on motor function were studied. Both GABA and sodium valproate inhibited in a dose dependent manner the hyperactivity induced by the bilateral injection of dopamine into the nucleus accumbens. Picrotoxin, a GABA antagonist, blocked the inhibitory effect of valproate. When injected into the pars reticulata of the substantia nigra, both sodium valproate and GABA enhanced apomorphine-induced circling in rats with a unilateral lesion of lateral hypothalamus caused by 6-hydroxydopamine. This effect was blocked by the systemic administration of picrotoxin. These observations suggest that sodium valproate can produce effects that result from the activation of GABA receptor sites in the brain.

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

  • Anlezark G, Horton RW, Meldrum BS, Sawaya MCB (1976) Anticonvulsant action of ethanolamine-o-sulphate and di-n-propylacetate and the metabolism of γ-aminobutyric acid (GABA) in mice with audiogenic seizures. Biochem Pharmacol 25:413–417

    Google Scholar 

  • Arnt J, Scheel-Krüger J (1979) GABA ergic and glycinergic mechanisms within the substantia nigra. Pharmacological specificity of dopamine independent contralateral turning behaviour and interactions with other neurotransmitters. Psychopharmacology 62:267–277

    Google Scholar 

  • DiChiara G, Morelli M, Porceddu ML, Gessa GL (1978) Evidence that nigrad GABA mediates behavioural responses elicited by striatal dopamine receptor stimulation. Life Sci 23:2045–2051

    Google Scholar 

  • DiChiara G, Porceddu ML, Mulas ML, Gessa GL (1979) Substantia nigra as an output station for striatal dopaminergic response. Role of GABA mediated inhibition of pars reticulata neurons. Naunyn-Schmiederberg's Arch Pharmacol 306:153–159

    Google Scholar 

  • Gale K, Iadarola MJ (1980) Seizure protection and increased nerveterminal GABA: Delayed effects of GABA transaminase inhibition. Science 208:288–291

    Google Scholar 

  • Garcia-Munoz M, Nicolaou NM, Tulloch IF, Wright AK, Arbuthnott GW (1977) Feedback loop or output pathway in strionigral fibres? Nature 265:363–364

    Google Scholar 

  • Hassan MN, Laljee HCK, Parsonage MJ (1976) Sodium valproate in the treatment of resistant epilepsy. Acta Neurol Scand 54: 209–218

    Google Scholar 

  • Henn FA, Hamberger A (1971) Glial cell function. Uptake of transmitter substances. Proc Nat Acad Sci USA 68:2686–2690

    Google Scholar 

  • Hökfelt T, Ljungdahl A, Perez de la Mora M, Fuxe K (1976) Further evidence that apomorphine increases GABA turnover in the DA cell body rich and DA nerve terminal rich areas of the brain. Neurosci Letters 2:239–242

    Google Scholar 

  • Horton RW, Anlezark GM, Sawaya MCB, Meldrum BS (1977) Monamine and GABA metabolism and the anticonvulsant action of di-n-propylacetate and ethanolamine-o-sulphate. Eur J Pharmacol 41:387–397

    Google Scholar 

  • Iversen LL (1971) Role of transmitter uptake mechanisms in synaptic neurotransmission. Br J Pharmacol 41:571–591

    Google Scholar 

  • Kerwin RW, Carter C, Pyrock C (1979) A comparison of l- and d-baclofen on dopamine dependent behaviour in the rat. Neuropharmacology 18:655–659

    Google Scholar 

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

    Google Scholar 

  • Kupferberg HL, Lust WD, Perry JK (1975) Anticonvulsant activity of dipropyl acetic acid (DPA) in relation to GABA and cGMP brain levels in mice. Fed Proc 34:283

    Google Scholar 

  • Marshall TF, Ungerstedt U (1977) Striatal efferent fibres play a role in maintaining rotational behaviour in the rat. Science 198:62–64

    Google Scholar 

  • Martin DL (1976) Carrier mediated transport and removal of GABA from synaptic regions. In: Roberts E, Chase TN, Tower DB (eds) GABA in nervous system function. Raven Press, New York

    Google Scholar 

  • Martin GE, Papp NL, Bacino CB (1978) Contralateral turning evoked by the intranigral microinjection of muscimol and other GABA agonists. Brain Res 155:297–312

    Google Scholar 

  • Olianas MC, Graziella M, Demontis MG, Tagliamonte A (1978) The striatal dopaminergic function is mediated by the inhibition of a nigral, nondopaminergic neuronal system via a strio-nigral gabergic pathway. Eur J Pharmacol 49:233–241

    Google Scholar 

  • Olpe HR, Schellenberg H, Kobela WP (1977) Rotational behaviour induced in rats by intranigral application of GABA related drugs and GABA antagonists. Eur J Pharmacol 45:291–294

    Google Scholar 

  • Pijnenburg ALJ, Van Rossum JM (1973) Stimulation of locomotor activity following injection of dopamine into nucleus accumbens. J Pharm Pharmacol 25:1003–1005

    Google Scholar 

  • Pinder RM, Brogden RN, Speight TM, Avery GS (1977) Sodium valproate: A review of its pharmacological properties and therapeutic efficacy in epilepsy. Drugs 13:81–123

    Google Scholar 

  • Pycock CL, Horton RW (1976) Possible GABA mediated control of dopamine-dependent behavioural effects from the nucleus accumbens of the rat. Psychopharmacology 49:173–179

    Google Scholar 

  • Pycock CL, Horton RW (1979) Dopamine dependent hyperactivity in the rat following manipulation of GABA mechanisms in the region of the nucleus accumbens. J Neural Trans 45:17–33

    Google Scholar 

  • Scheel-Krüger J, Arnt J, Magelund G (1977b) Behavioural stimulation induced by muscimol and other GABA agonists injected into the substantia nigra. Neurosci Letters 4:351–356

    Google Scholar 

  • Scheel-Krüger J, Cools AR, Honig W (1977a) Muscimol antagonizes the ergometrine induced locomotor activity in nucleus accumbens: Evidence for GABA-dopaminergic interaction. Eur J Pharmacol 42:311–313

    Google Scholar 

  • Simler S, Ciesieleski L, Maitre M, Randrianarisoa H, Mandel P (1973) Effect of sodium di-n-propylacetate on audiogenic seizures and brain gamma-aminobutyric acid levels. Biochem Pharmacol 22:1701–1708

    Google Scholar 

  • Simon D, Perry JK (1975) Sodium-di-n-propylacetate (DPA) in the treatment of epilepsy. A review. Epilepsia 16:549–573

    Google Scholar 

  • Ungerstedt U (1971) Postsynaptic supersensitivity after 6-hydroxydopamine induced degeration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl 367:69–73

    Google Scholar 

  • Van Der Laan JW, DeBoer TH, Bruinvels J (1979) Di-n-propylacetate and GABA degradation. Preferential inhibition of succinic semialdehyde dehydrogenase and indirect inhibition of GABA-transaminase. J Neurochem 32:1869–1880

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kuruvilla, A., Uretsky, N.J. Effect of sodium valproate on motor function regulated by the activation of GABA receptors. Psychopharmacology 72, 167–172 (1981). https://doi.org/10.1007/BF00431651

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00431651

Key words

Navigation