Purpose: It has been suggested that nitric oxide (NO) is involved in sleep
mechanisms and in the pathophysiology of epilepsy. Data are, however, contr
oversial because it is not clear whether NO facilitates sleep or waking, or
whether it exerts pro- or antiepileptic influences.
Methods: The question was considered through NO voltammetric measurements a
nd electroencephalographic recordings performed in GAERS rats (Genetic Abse
nce Epilepsy Rat from Strasbourg): an experimental model of "petit-mal" hum
an disease. Regulatory processes of sleep and epilepsy were studied after a
dministration of a NO synthase inhibitor [L-arginine-pnitroanilide (L-ANA)
100 mg/kg i.p.], a NO donor(SIN-1 100 ng/2 mu l i.c.v.), and the antiepilep
tic drugs used in clinic [valproate (VPA 200 mg/kg i.p.) and ethosuximide (
ESM 100 mg/kg i.p.)].
Results: In GAERS rats, spontaneous circadian organizations of spike-wave d
ischarges and paradoxical sleep (PS) occur in an opposite way; spontaneous
NO concentrations are higher during seizures than during wakefulness, slow-
wave sleep, and PS, respectively. L-ANA induces a disappearance of NO peak,
an epileptic induction, and a loss of PS while SIN-1 induces opposite effe
cts. Antiepileptic effects of VPA and ESM are associated with a PS increase
and a significant release of NO.
Conclusions: These results indicate that NO could be, in GAERS rats, a cent
ral piece in the reciprocal inhibitory mechanisms regulating the induction
of PS and spike-wave discharges. NO could prevent absence epilepsy and act
as an antiepileptic substance in facilitating PS. Antiepileptic efficiency
of VPA and ESM may work through their ability to release NO. A track for a
new treatment of petit-mal disease in children can be envisioned.