Experimental manipulations of the subthalamic nucleus fail to suppress tonic seizures in the electroshock model of epilepsy
Author: Shehab SA, Ljubisavljevic M, Al Halhali F, Al Awadhi A, Madathil M, Abdul Kareem A, Redgrave P.
Source:
Experimental brain research, 173(2), 274-281.
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.