Anticonvulsant and proconvulsant roles of nitric oxide in experimental epilepsy models

Abstract

The effect of acute (120 mg/kg) and chronic (25 mg/kg, twice a day, for 4 days) intraperitonial injection of the nitric oxide (NO) synthase (NOS) inhibitor N G -nitro-L-arginine (L-NOARG) was evaluated on seizure induction by drugs such as pilocarpine and pentylenetetrazole (PTZ) and by sound stimulation of audiogenic seizure-resistant (R) and audiogenic seizure-susceptible (S) rats. Seizures were elicited by a subconvulsant dose of pilocarpine (100 mg/kg) only after NOS inhibition. NOS inhibition also simultaneously potentiated the severity of PTZ-induced limbic seizures (60 mg/kg) and protected against PTZ-induced tonic seizures (80 mg/kg). The audiogenic seizure susceptibility of S or R rats did not change after similar treatments. In conclusion, proconvulsant effects of NOS inhibition are suggested to occur in the pilocarpine model and in the limbic components of PTZinduced seizures, while an anticonvulsant role is suggested for the tonic seizures induced by higher doses of PTZ, revealing inhibitorspecific interactions with convulsant dose and also confirming the hypothesis that the effects of NOS inhibitors vary with the model of seizure.

Do endogenous opioids and nitric oxide participate in the anticonvulsant action of dipyrone?

“…However, our results showed that acute or chronic L-NOARG treatment did not reverse the anticonvulsant effect of dipyrone in Wistar audiogenic rats, suggesting that the NO pathway is not involved in the mechanism of anticonvulsant action of dipyrone in audiogenic seizures. Del-Bel et al (20) reported that audiogenic seizure-resistant rats did not modify their behavior after L-NOARG-induced systemic NO synthase blockade. Also, GEPR-3s (genetically epilepsy-prone rats), Sprague-Dawley-derived rats of the so-called mild subcolony (in contrast to GEPR-9s, severe subcolony) that display audiogenic seizures when sound-stimulated (21,22), did not exhibit changes in seizure severity or in the mean latencies of wild running or tonicclonic seizure after acute or chronic L-NOARG treatment (23).…”

A comparative experimental study of proconvulsive potential of ciprofloxacin and ofloxacin and assessment of proconvulsive potentiating action of caffeine coadministration with fluoroquinolones in rats

“…The dose of the drug(s) which increased the duration of THLE and duration of clonic convulsions was considered to have proconvulsant activity. [11] In the chemoconvulsion model, the incidence of seizures (1 = present, 0 = absent), Grade of convulsions (according to racene scale), [14] and the onset of Grade 3 convulsions (seconds) were noted. [14,15] Grading of convulsions according to Racene scale were as follows: 0 = no response, 1 = ear/mouth/facial twitchings, 2 = head nodding, 3 = forelimb clonus/body jerks, 4 = rearing, 5 = rearing, and falling down with/without generalized convulsions.…”

“…[11] In the chemoconvulsion model, the incidence of seizures (1 = present, 0 = absent), Grade of convulsions (according to racene scale), [14] and the onset of Grade 3 convulsions (seconds) were noted. [14,15] Grading of convulsions according to Racene scale were as follows: 0 = no response, 1 = ear/mouth/facial twitchings, 2 = head nodding, 3 = forelimb clonus/body jerks, 4 = rearing, 5 = rearing, and falling down with/without generalized convulsions. [14,15] Higher incidence of seizures, higher grading of seizures, and reduction in onset of Grade 3 convulsions were considered as proconvulsant activity.…”

“…[14,15] Grading of convulsions according to Racene scale were as follows: 0 = no response, 1 = ear/mouth/facial twitchings, 2 = head nodding, 3 = forelimb clonus/body jerks, 4 = rearing, 5 = rearing, and falling down with/without generalized convulsions. [14,15] Higher incidence of seizures, higher grading of seizures, and reduction in onset of Grade 3 convulsions were considered as proconvulsant activity. [14,15] Statistical analysis was done using one-way ANOVA, and post hoc test done by least significant difference method.…”

“…[14,15] Higher incidence of seizures, higher grading of seizures, and reduction in onset of Grade 3 convulsions were considered as proconvulsant activity. [14,15] Statistical analysis was done using one-way ANOVA, and post hoc test done by least significant difference method. SPSS v19 was employed for statistical analysis.…”