Glutaric acidaemia type I (GA-I) is a cerebral organic disorder characterized by the accumulation of
glutaric acid (GA) and
seizures. As
seizures are precipitated in children with GA-I and the mechanisms underlying this disorder are not well established, we decided to investigate the role of
nitric oxide (NO) in GA-induced convulsive behaviour in pup rats. Pup male Wistar rats (18-day-old) were anesthetized and placed in stereotaxic apparatus for
cannula insertion into the striatum for injection of GA. The experiments were performed 3 days after surgery (pup rats 21-day-old). An inhibitor of NO synthesis (
N-G-nitro-l-arginine methyl ester-
L-NAME, 40 mg/kg) or saline (vehicle) was administered intraperitoneally 30 min before the intrastriatal injection of GA (1 µl, 1.3 µmol/striatum) or saline. Immediately after the intrastriatal
injections, the latency and duration of
seizures were recorded for 20 min. The administration of
L-NAME significantly increased the latency to the first seizure episode and reduced the duration of
seizures induced by GA in pup rats. The administration of the NO precursor
l-arginine (L-ARG; 80 mg/kg) prevented the effects of
L-NAME. Besides, GA significantly increased
nitrate and
nitrite (NOx) levels in the striatum of pup rats and the preadministration of
L-NAME prevented this alteration. L-ARG blocked the reduction of striatal NOx provoked by
L-NAME. These results are experimental evidence that NO plays a role in the
seizures induced by GA in pup rats, being valuable in understanding the physiopathology of neurological signs observed in children with this organic acidaemia and to develop new therapeutic strategies.