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

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.

Pharmacological evidence for an anticonvulsant relay in the rat ventromedial medulla

“…In the present case of injections of NMDA and muscimol failing to elicit similar anticonvulsant effects, it is proper to consider whether appropriate doses and an optimal delay before testing were used. Firstly, in the present study the drug doses were similar to those reported by other investigators (Kinjo et al, 1990;Depaulis et al, 1994;Dybdal & Gale, 2000;Shehab et al, 2006). Secondly, in pilot investigations to establish appropriate drug dosages for the present study, larger doses of NMDA (10 mm) and muscimol (200-400 pmol) resulted in the death of most subjects tested.…”

How do seizures stop?

“…Smaller projections arriving from brainstem areas of substantia nigra, pendunculopontine nucleus, and raphe nuclei bring dopaminergic, cholinergic, and serotonergic activity that modulates STN activity (Hamani et al., 2004). Microinfusion of muscimol into STN raises the threshold for seizures in some, but not all animal models (Veliskova et al., 1996; Shehab et al., 2006). Electrical stimulation of the STN in rodents, and humans, raises the seizure threshold and has an anticonvulsant effect (Chabardes et al., 2002; Lado et al., 2003).…”

Neuroprotective Effect of Curcumin on the Nigrostriatal Pathway in a 6-Hydroxydopmine-Induced Rat Model of Parkinson’s Disease is Mediated by α7-Nicotinic Receptors

“…injection of an equal mixture of ketamine hydrochloride (80 mg/kg, Troy Laboratory PTY Limited Glendenning, NSW, Australia) and xylazine hydrochloride (20 mg/kg, Troy Laboratory PTY Limited Glendenning, NSW, Australia). To lesion the nigrostriatal pathway, the heads of the animals were shaved and placed into a Stoelting stereotaxic frame and a unilateral hole on the right side of the skull was made as described before [ 67 ], aiming at the striatum. The rats received unilateral injections of 6-OHDA at three distinct locations within the caudate-putamen (7 µg in each site).…”