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.

Local disinhibition of several interconnected regions in the brainstem of rats, including the dorsal midbrain, the mesencephalic locomotor region and the ventrolateral pontine reticular formation, has anticonvulsant properties in the maximal electroshock model of epilepsy. A recent anatomical study [Shehab, S., McGonigle, D., Hughes, D., Todd, A. & Redgrave, P. (2005) Eur. J. Neurosci., 22, 1431-1444.] revealed significant anatomical connections between an anticonvulsant relay region in the ventrolateral pons and reticulospinal projection neurons in the ventromedial medullary reticular formation. This pathway was shown to have both glutamatergic and GABAergic components. The purpose of the present study was to test whether local excitation or inhibition directed to the target zone of this projection in the ventral medulla would also have anticonvulsant properties. Neural excitation induced by local bilateral injections of the GABA(A) antagonist bicuculline into the ventromedial medulla caused a reliable dose-related suppression of hindlimb extension in the maximal electroshock test. The anticonvulsant effect of bicuculline was significantly greater in the terminal zone of the afferent projection from the ventral pons than that observed in adjacent tissue. Neither direct excitation following injections of N-methyl-D-aspartate nor direct inhibition by injections of the GABA agonist muscimol into the same region had reliable anticonvulsant effects. A statistically reliable association was observed between the anticonvulsant and locomotor activation effects of injections of bicuculline into the ventral medulla. No such relationship was found with bicuculline-induced disturbances of muscle tone, as reflected by the presence of postural dysfunction. Together these data establish the final functional link connecting brainstem anticonvulsant circuitry with reticulospinal systems controlling hindlimb musculature.