Experimental manipulations of the subthalamic nucleus fail to suppress tonic seizures in the electroshock model of epilepsy.

Full Abstract

Recently, it has been shown that the subthalamic nucleus (STN) has anticonvulsant effects on epileptic seizures originating from the forebrain. The aim of the present study was to determine whether the anticonvulsant properties of the STN extend to the suppression of tonic seizures originating from the brainstem elicited by electroshock in rats. Three different procedures were used to manipulate activity in the STN and in each case the duration of tonic hindlimb extension elicited by electroshock was used as a measure of seizure-severity. Under general anesthesia, two groups of rats received chronic implants of either bilateral stainless steel guide cannulae or bilateral bipolar stimulating electrodes stereotaxically implanted and aimed at the STN. After 3 days of recovery, each rat in the first group was tested with electroshock on three consecutive days after having received 220 nl bilateral microinjections into the STN of either 200 or 400 pmol of muscimol (a GABA agonist) dissolved in saline or the same volume of normal saline. In the second group the electroshock test was conducted, again on three consecutive days, immediately following high frequency electrical stimulation (HFS) of the STN at 130 or 260 Hz or a no current control condition. In the third group, rats were tested with electroshock before and after bilateral excitotoxic lesions of the STN with either kainic or ibotenic acids. None of these manipulations produced significant suppression of the tonic hind limb extension elicited by electroshock compared with the relevant control conditions. This suggests that, within the limitations of the current procedures, the anticonvulsant properties of the STN appear to be ineffective against tonic seizures originating in the brainstem.

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Author information

Author/s: Shehab, S A S (SA); Ljubisavljevic, M (M); Al-Halhali, F (F); Al-Awadhi, A (A); Madathil, M (M); Abdul-Kareem, A (A); Redgrave, P (P);

Affiliation: Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al-Ain, UAE. s.shehab(-atsign-)uaeu.ac.ae

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale (Exp Brain Res), published in Germany. (Language: eng)

Reference: 2006-Aug; vol 173 (issue 2) : pp 274-81

Dates: Created 2006/08/09; Completed 2006/11/07; Revised 2008/02/15;

PMID: 16676172, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Behavior, Animal - drug effects; physiology
Electric Stimulation
Electrodes, Implanted
Electroshock
Epilepsy, Generalized - physiopathology
Female
GABA Agonists - administration & dosage; pharmacology
Immunohistochemistry

Immunohistochemistry
Male
Microinjections
Muscimol - administration & dosage; pharmacology
Proto-Oncogene Proteins c-fos - biosynthesis
Rats
Rats, Wistar
Seizures - physiopathology
Subthalamic Nucleus - drug effects; physiology

Associated Chemicals: GABA Agonists (0) ; Proto-Oncogene Proteins c-fos (0) ; Muscimol (2763-96-4)

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