+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Effects of gamma-aminobutyric acid (GABA) agonists and a GABA uptake inhibitor on pharmacoresistant seizure like events in organotypic hippocampal slice cultures

Effects of gamma-aminobutyric acid (GABA) agonists and a GABA uptake inhibitor on pharmacoresistant seizure like events in organotypic hippocampal slice cultures

Epilepsy Research 86(2-3): 113-123

Seizure like events (SLEs) induced by low magnesium or 4-aminopyridine in organotypic hippocampal slice cultures (OHSCs) are resistant to standard antiepileptic drugs including phenobarbital, and 1,4-benzodiazepines [Albus, K., Wahab, A., Heinemann, U., 2008. Standard antiepileptic drugs fail to block epileptiform activity in rat organotypic hippocampal slice cultures. Br. J. Pharmacol. 154, 709-724]. The present study was undertaken in order to test the effects of other compounds on SLEs in OHSCs that enhance GABA-mediated actions. Six to 12 days old Wistar rats were used to cultivate OHSCs according to the interface method [Stoppini, L., Buchs, P.A., Muller, D., 1991. A simple method for organotypic cultures of nervous tissue. J. Neurosci. Methods 37, 173-182]. Neuronal activity and extracellular potassium concentration were recorded under submerged conditions. SLEs were induced by lowering the magnesium concentration. The effects of GABA(A) agonists muscimol and isoguvacine, the GABA(B) agonist baclofen, the GABA uptake blocker nipecotic acid and the neurosteroid alfaxalone on induction and ongoing SLEs were analyzed. Low magnesium induced SLEs were dose dependently suppressed by the GABA(A) receptor agonists muscimol, isoguvacine and alfaxalone and by the GABA uptake inhibitor nipecotic acid whereas the GABA(B) receptor agonist baclofen attenuated but did not suppress SLE. Our findings demonstrate that in OHSCs GABA has an inhibitory effect on SLEs. Proconvulsant effects of GABA agonists on spontaneous neuronal activity and seizure like activity were never observed. Our findings exclude a possible contribution of impaired/altered GABA-ergic mechanisms based on immaturity of receptors and/or low receptor density to seizure susceptibility and pharmacoresistance in OHSCs.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 052868173

Download citation: RISBibTeXText

PMID: 19535226

DOI: 10.1016/j.eplepsyres.2009.05.008

Related references

Effects of gamma-aminobutyric acid (GABA) agonists and GABA uptake inhibitors on pharmacosensitive and pharmacoresistant epileptiform activity in vitro. British Journal of Pharmacology 119(3): 569-577, 1996

Use of gamma-aminobutyric acid (GABA)-transaminase inhibitors and a GABA uptake inhibitor to investigate the influence of GABA neurons on dopamine-containing amacrine cells of the rat retina. Journal of Pharmacology and Experimental Therapeutics 227(3): 627-632, 1983

Effect of glutamate decaboxylase- and GABA transaminase-inhibitors on the GABA (.GAMMA.-aminobutyric acid) level in the isolated pancreatic islets and the hippocampal slice of the rat in vitro. Proceedings of the Japan Academy Series B Physical and Biological Sciences 56(1): 46-50, 1980

Effect of thyrotropin releasing hormone (TRH) on GABA (gamma aminobutyric acid) metabolism in mouse and rat brains: as to the activities of GAD (glutamic acid decarboxylase), GABA-T (GABA-transaminase) and GABA re-uptake. No to Shinkei 37(12): 1211-1216, 1985

Effects of the GABA uptake inhibitor tiagabine on inhibitory synaptic potentials in rat hippocampal slice cultures. Journal of Neurophysiology 67(6): 1698-1701, 1992

The gamma-aminobutyric acid (GABA) uptake inhibitor, tiagabine, increases extracellular brain levels of GABA in awake rats. European Journal of Pharmacology 220(2-3): 197-201, 1992

Inhibition of transporter mediated gamma-aminobutyric acid (GABA) release by SKF 89976-A, a GABA uptake inhibitor, studied in a primary neuronal culture from chicken. Neurochemical Research 17(6): 577-584, 1992

Engineered Zn(2+) switches in the gamma-aminobutyric acid (GABA) transporter-1. Differential effects on GABA uptake and currents. Journal of Biological Chemistry 276(44): 40476-40485, 2001

The physiological significance of gamma-aminobutyric acid (GABA) in brain function. I. The pharmacological similarity of alpha-chloro-gamma-aminobutyric acid (alpha-CI-GABA) to gamma-aminobutyric acid (GABA). Nihon Seirigaku Zasshi. Journal of the Physiological Society of Japan 30(2): 109-113, 1968

Audiogenic seizure protection by elevated brain GABA concentration in mice: effects of gamma-acetylenic gaba and gamma-vinyl GABA, two irreversible GABA-T inhibitors. European Journal of Pharmacology 45(4): 319-328, 1977

gamma-Aminobutyric acid (GABA) signaling components in Drosophila: immunocytochemical localization of GABA(B) receptors in relation to the GABA(A) receptor subunit RDL and a vesicular GABA transporter. Journal of Comparative Neurology 505(1): 18-31, 2007

The irreversible gamma-aminobutyric acid (GABA) transaminase inhibitor gamma-vinyl-GABA blocks cocaine self-administration in rats. Journal of Pharmacology and Experimental Therapeutics 290(2): 797-802, 1999

Effect of dopamine agonists on gamma-aminobutyric acid (GABA) turnover in the superior colliculus: evidence that nigrotectal GABA projections are under the influence of dopaminergic transmission. Journal of Pharmacology and Experimental Therapeutics 226(2): 425-431, 1983

Ischaemia differentially regulates GABA(B) receptor subunits in organotypic hippocampal slice cultures. Neuropharmacology 56(8): 1088-1096, 2009

The effect of NOS inhibiton on GABA and glutamate release in human hippocampal organotypic slice cultures. Epilepsia 44(Suppl. 9): 45, 2003