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Effectiveness of vigabatrin against focally evoked pilocarpine-induced seizures and concomitant changes in extracellular hippocampal and cerebellar glutamate, gamma-aminobutyric acid and dopamine levels, a microdialysis-electrocorticography study in freely moving rats.
J Pharmacol Exp Ther. 1997 Dec; 283(3):1239-48.JP

Abstract

Limbic seizures were evoked in freely moving rats by intrahippocampal administration of the muscarinic agonist pilocarpine via the microdialysis probe (10 mM for 40 min at 2 microl/min). This study monitored changes in extracellular hippocampal gamma-aminobutyric acid (GABA), glutamate and dopamine levels after systemic (30 mg/kg/day) or local (intrahippocampal or intranigral, 5 mM or 600 microM for 180 min at 2 microl/min) vigabatrin administration, and evaluated the effectiveness of this antiepileptic drug against pilocarpine-induced seizure activity. Extracellular GABA and glutamate overflow in the ipsilateral cerebellum was studied simultaneously. Microdialysis was used as an in vivo sampling technique and as a drug-delivery tool. Electrophysiological evidence for the presence or absence of seizures was recorded with electrocorticography. The observed alterations in extracellular hippocampal amino acid levels support the hypothesis that muscarinic receptor stimulation by the intrahippocampal administration of 10 mM pilocarpine is responsible for the seizure onset, and that the amino acids maintain the sustained seizure activity. The focally evoked pilocarpine-induced seizures were completely prevented by intraperitoneal vigabatrin premedication for 7 days or by a single intraperitoneal injection. Effective protection was reflected in a lack of sustained elevations of hippocampal glutamate levels. Rats receiving vigabatrin intrahippocampally or intranigrally still developed seizures, although there appeared to be a partial protective effect. During the intrahippocampal perfusion with 5 mM vigabatrin, extracellular hippocampal GABA levels increased, whereas the extracellular glutamate and dopamine overflow decreased. The lack of a complete neuroprotection after local vigabatrin treatment is discussed.

Authors+Show Affiliations

Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9399999

Citation

Smolders, I, et al. "Effectiveness of Vigabatrin Against Focally Evoked Pilocarpine-induced Seizures and Concomitant Changes in Extracellular Hippocampal and Cerebellar Glutamate, Gamma-aminobutyric Acid and Dopamine Levels, a Microdialysis-electrocorticography Study in Freely Moving Rats." The Journal of Pharmacology and Experimental Therapeutics, vol. 283, no. 3, 1997, pp. 1239-48.
Smolders I, Khan GM, Lindekens H, et al. Effectiveness of vigabatrin against focally evoked pilocarpine-induced seizures and concomitant changes in extracellular hippocampal and cerebellar glutamate, gamma-aminobutyric acid and dopamine levels, a microdialysis-electrocorticography study in freely moving rats. J Pharmacol Exp Ther. 1997;283(3):1239-48.
Smolders, I., Khan, G. M., Lindekens, H., Prikken, S., Marvin, C. A., Manil, J., Ebinger, G., & Michotte, Y. (1997). Effectiveness of vigabatrin against focally evoked pilocarpine-induced seizures and concomitant changes in extracellular hippocampal and cerebellar glutamate, gamma-aminobutyric acid and dopamine levels, a microdialysis-electrocorticography study in freely moving rats. The Journal of Pharmacology and Experimental Therapeutics, 283(3), 1239-48.
Smolders I, et al. Effectiveness of Vigabatrin Against Focally Evoked Pilocarpine-induced Seizures and Concomitant Changes in Extracellular Hippocampal and Cerebellar Glutamate, Gamma-aminobutyric Acid and Dopamine Levels, a Microdialysis-electrocorticography Study in Freely Moving Rats. J Pharmacol Exp Ther. 1997;283(3):1239-48. PubMed PMID: 9399999.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effectiveness of vigabatrin against focally evoked pilocarpine-induced seizures and concomitant changes in extracellular hippocampal and cerebellar glutamate, gamma-aminobutyric acid and dopamine levels, a microdialysis-electrocorticography study in freely moving rats. AU - Smolders,I, AU - Khan,G M, AU - Lindekens,H, AU - Prikken,S, AU - Marvin,C A, AU - Manil,J, AU - Ebinger,G, AU - Michotte,Y, PY - 1998/2/12/pubmed PY - 1998/2/12/medline PY - 1998/2/12/entrez SP - 1239 EP - 48 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 283 IS - 3 N2 - Limbic seizures were evoked in freely moving rats by intrahippocampal administration of the muscarinic agonist pilocarpine via the microdialysis probe (10 mM for 40 min at 2 microl/min). This study monitored changes in extracellular hippocampal gamma-aminobutyric acid (GABA), glutamate and dopamine levels after systemic (30 mg/kg/day) or local (intrahippocampal or intranigral, 5 mM or 600 microM for 180 min at 2 microl/min) vigabatrin administration, and evaluated the effectiveness of this antiepileptic drug against pilocarpine-induced seizure activity. Extracellular GABA and glutamate overflow in the ipsilateral cerebellum was studied simultaneously. Microdialysis was used as an in vivo sampling technique and as a drug-delivery tool. Electrophysiological evidence for the presence or absence of seizures was recorded with electrocorticography. The observed alterations in extracellular hippocampal amino acid levels support the hypothesis that muscarinic receptor stimulation by the intrahippocampal administration of 10 mM pilocarpine is responsible for the seizure onset, and that the amino acids maintain the sustained seizure activity. The focally evoked pilocarpine-induced seizures were completely prevented by intraperitoneal vigabatrin premedication for 7 days or by a single intraperitoneal injection. Effective protection was reflected in a lack of sustained elevations of hippocampal glutamate levels. Rats receiving vigabatrin intrahippocampally or intranigrally still developed seizures, although there appeared to be a partial protective effect. During the intrahippocampal perfusion with 5 mM vigabatrin, extracellular hippocampal GABA levels increased, whereas the extracellular glutamate and dopamine overflow decreased. The lack of a complete neuroprotection after local vigabatrin treatment is discussed. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/9399999/Effectiveness_of_vigabatrin_against_focally_evoked_pilocarpine_induced_seizures_and_concomitant_changes_in_extracellular_hippocampal_and_cerebellar_glutamate_gamma_aminobutyric_acid_and_dopamine_levels_a_microdialysis_electrocorticography_study_in_freely_moving_rats_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9399999 DB - PRIME DP - Unbound Medicine ER -