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Nitric oxide synthesis, epileptic seizures and kindling

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Abstract

Nitric oxide (NO) has been implicated in synaptic changes underlying long-term potentiation and some forms of learning. It is unclear, however, whether NO contributes to long-term changes associated with the kindling of epileptic seizures. In the present study rats were treated, on the first 6 days of kindling, withl-arginine (l-Arg), the endogenous donor from which NO derives, or withl-nitro-arginine (l-No-Arg), a competitive inhibitor of NO synthesis, or with vehicle. Drugs were given in doses previously shown to affect learning or other behaviour.l-Arg (750 mg/kg IP) did not affect kindling or seizure severity.l-No-Arg (100 mg/kg) prolonged the duration of afterdischarges and convulsions on treatment days but did not advance kindling or affect seizures on subsequent days. A second experiment examined the possible rôle of NO in the development of resistance to seizures following prior seizures. Six or more stimuli were administered at 10-min intervals to fully-kindled rats after injection ofl-No-Arg or vehicle. Vehicle-treated rats became progressively more resistant to afterdischarges and convulsions with successive stimulations butl-No-Arg-treated rats failed to do so. Rats injected withl-No-Arg also showed an unexpected high mortality in the ensuing 24 h.l-No-Arg appeared to have no direct effect on the course of kindling but impaired the development of postictal resistance, and increased the duration and lethal after-effects of closely repeated seizures. The results do not support suggestions that antagonists of NO might prove clinically useful as anticonvulsants.

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  1. Institute of Neurology, Queen Square, WC1N 3BG, London, UK

    L. J. Herberg, A. Grottick & I. C. Rose

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  1. L. J. Herberg
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  2. A. Grottick
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Herberg, L.J., Grottick, A. & Rose, I.C. Nitric oxide synthesis, epileptic seizures and kindling. Psychopharmacology 119, 115–123 (1995). https://doi.org/10.1007/BF02246062

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