Summary
Rats were exposed for 24 min to bilateral clamping of the common carotid arteries (BCCA) in pentobarbital anaesthesia. 14 days later the animals were subjected to subcutaneous injection of (+)-bicuculline (3 or 4 mg/kg). A significantly decreased susceptibility to bicuculline-induced seizures could be observed in BCCA treated rats compared with sham operated controls. It is suggested that BCCA treatment protects animals against status epilepticus and lethal toxicity produced by bicuculline. Electrographic recordings of the BCCA animals revealed no ictal activity within 1 h after bicuculline injection. An analysis of the GABA content showed a significant increase in the hippocampus (HPC), frontal cortex (FCX), parietal cortex and substantia nigra in BCCA animals compared with controls. It is therefore possible that an increase in GABA content postsynaptically counteracts the GABAA antagonistic effect of bicuculline in BCCA animals thus preventing the normal seizure inducing effect of this substance.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baxter CT (1976) Some recent advantages in studies of GABA metabolism and compartmentation. In: Roberts E, Chase TN, Tower DB (eds) GABA in nervous system function. Raven Press, New York, pp 61–87
Blennow G, Brierley JB, Meldrums BS, Siesjö BK (1978) Epileptic brain damage. The role of systemic factors that modify cerebral energy metabolism. Brain 101: 687–700
Block F, Heim C, Korf J, Sieklucka M, Sontag K-H (1989) Metabolic changes in selective vulnerable brain structures during and after bilateral clamping of both carotid arteries (BCCA) in normotensive rats. Eur J Neurosci [Suppl] 2: 151
Block F, Sontag K-H (1990) Electrophysiological and behavioural changes produced by 2 vessel occlusion (2VO) in the rat. Pflügers Arch 415 [Suppl 1]: R 89, 331
Burchfield JL, Duchowny MS, Duffy FM (1979) Neuronal supersensitivity to acetylcholine induced by kindling in the rat hippocampus. Science 204: 1096–1098
Cavalheiro EA, Riche D, Le Gal la Salle G (1982) Long-term effect of intrahippocampal kainic acid injection in rat: a method for inducing spontaneous recurrent seizures. Electroencephalogr Clin Neurophysiol 53: 581–589
Diedrichs S (1987) Paradoxe anticonvulsive Wirkung des GABAA-Antagonisten Bicucullin im Nucleus Caudatus-Putamen der Ratte: Eine Studie am Modell Pilocarpin-induzierter KrÄmpfe. Med Diss, University of Göttingen, Federal Republic of Germany
Fukuda H, Brailowsky S, Menini C, Silva-Barrat C, Riche D, Naquet R (1987) Anticonvulsant effect of intrastriatal, chronic infusion of GABA in kindled rats: focal seizures upon withdrawal. Exp Neurol 98: 120–129
Gale K (1985) Mechanism of seizure control mediated by γ-aminobutyric acid: role of the substantia nigra. Fed Proc 44: 2414–2424
Gale K, Iadarola MJ (1980) Seizure protection and increased nerve-terminal GABA: delayed effects of GABA transaminase inhibition. Science 208: 288–291
Heim C, Sontag K-H, Bortolotto Z, Sieklucka M, Turski L, Cavalheiro E, Klockgether T (1987) Increased threshold for limbic seizures induced by pilocarpine (PC) after bilateral clamping of carotid arteries (BCCA). Abstr of 10th IUPHAR Congress, Sydney, Australia, p 423
Heim C, Sieklucka-Dziuba M, Bortolotto ZA, Löscher W, Cavalheiro EA, Sontag K-H (1988) Is the protection against pilocarpine induced seizures after transient oligemic hypoxia caused by increased GABA-levels in different vulnerable structures? Psychopharmacology [Suppl 96]: 373 (Abstr 16th CINP Congress, Munich)
Iadarola MJ, Gale K (1982) Substantia nigra: site of anticonvulsant activity mediated by γ-aminobutyric acid. Science 218: 1237–1240
Kamphuis W, Huisman E, Wadman WJ, Lopes da Silva FH (1989) Decrease in GABA immunoreactivity and alteration of GABA metabolism after kindling in the rat hippocampus. Exp Brain Res 74: 375–386
Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239: 57–69
Kleinrok Z, Turski L (1980) Kainic acid induced wet-dog shakes in rats. The relation to central neurotransmitters. Naunyn-Schmiedebergs Arch Pharmacol 314: 37–46
Le Gal la Salle G, Brailowsky S, Menini CH, Naquet R (1988) Local asymptomatic status epilepticus induced by withdrawal of GABA infusion into limbic structures. Exp Neurol 1: 411–417
Lindgren S, Simmons MA (1987) Adaptation of the GABAA receptor complex in rat brain during chronic elevation of GABA by ethanolamin-O-sulphat. Br J Pharmacol 91: 617–625
Löscher W (1980) A comparative study of the pharmacology of inhibitors of GABA-metabolism. Naunyn Schmiedebergs Arch Pharmacol 315: 119–128
Löscher W, Vetter M (1984) Relationship between drug-induced increases of GABA levels in discrete brain areas and different pharmacologial effects in rats. Biochem Pharmacol 33: 1907–1914
Lowe JP, Robins E, Eyerman GS (1958) The fluorimetric measurements of glutamic decarboxylase and its distribution in brain. J Neurochem 3: 8–18
Meldrum BS (1975) Epilepsy and γ-aminobutyric acid-mediated inhibition. Int Rev Neurobiol 17: 1–36
Meldrum BS (1982) Pharmacology of GABA. Clin Neuropharmacol 6: 293–316
Pellegrino LJ, Cushman AJ (1967) A stereotaxic atlas of the rat brain. Plenum Press, New York
Piredda S, Gale K (1985) A crucial epileptogenic site in the deep prepiriform cortex. Nature (London) 317: 623–625
Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32: 281–294
Schechter PJ, Trainer Y, Jung MH, Sjoerdsma A (1977) Antiseizure activity of γ-acetylenic γ-aminobutyric acid: a catalytic irreversible inhibitor of γ-aminobutyric acid transaminase. J Pharmacol Exp Ther 201: 606–612
Schmidt-Kastner R, Hossmann K-A (1988) Distribution of ischemic neuronal damage in the dorsal hippocampus of rats. Acta Neuropathol 76: 411–421
Sutton J, Shnmonds M (1974) Effects of acute and chronic pentobarbitone on the γ-aminobutyric acid system in rat brain. Biochem Pharmacol 23: 1801–1808
Tower DB (1976) GABA and seizures: clinical correlates in man. In: Roberts C, Chase TN, Tower DB (eds) GABA in nervous system function. Raven Press, New York, pp 461–478
Turski WA, Cavalheiro EA, Calderazzo-Filho LS, Kleinrock Z, Czuczwar SJ, Turski L (1985) Injections of picrotoxine and bicuculline into the amygdaloid complex of the rat: an electroencephalographic, behavioural and morphological analysis. Neuroscience 14: 37–53
Turski L, Dietrichs S, Sieklucka M, Heim C, Schwarz M, Klockgether T, Sontag K-H, Bortolotto Z, Calderazzo-Filho LS, Cavalheiro EA (1987) Microinjections of γ-aminobutyrate antagonist bicuculline methiodide, into the caudate-putamen prevent pilocarpine-induced seizures in rats. Abstr 10th IUPHAR Congress, Sydney, Australia, p 420
Turski L, Cavalheiro EA, Calderazzo-Filho LS, Bortolotto ZA, Klockgether T, Ikonomidou C, Turski WA (1989) The basal ganglia, the deep prepiriform cortex, and seizure spread: bicuculline is anticonvulsant in the rat striatum. Proc Natl Acad Sci USA 86: 1694–1697
Wood JD, Watson WJ, Ducker AJ (1968) The effect of hypoxia an brain γ-aminobutyric acid levels. J Neurochem 15: 603–608
Author information
Authors and Affiliations
Additional information
Supported by Deutsche Forschungsgemeinschaft, SFB 330, Organprotektion
Rights and permissions
About this article
Cite this article
Sieklucka, M., Bortolotto, Z., Heim, C. et al. Decreased susceptibility to seizures induced by bicuculline after transient bilateral clamping of the carotid arteries in rats. J. Neural Transmission 83, 127–137 (1991). https://doi.org/10.1007/BF01244459
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01244459