Regular and lasting neocortical spiking produced by systemic administration of a steroid derivative in the rat.
The hypothesis was tested that sedation and stereotyped behaviour, developing in rats after the administration of the steroid derivative with gamma-aminobutyric acid (GABA) antagonistic properties, R 5135, are of an epileptiform nature. Electroencephalographic (EEG) and visual evoked potentials (VEP) were recorded and behaviour was observed over not less than 5-7 hr after subconvulsive doses of R 5135. Doses of 2-4 mg/kg of the compound produced quasi-rhythmic spikes resembling experimental focal epileptic discharges in all rats. This epileptiform activity was accompanied by behavioural sedation and somnolence, followed by a build-up of stereotyped behaviour and sporadic episodes of epileptiform motor activity, developing 1-2 hr after injection. The secondary components (SNW) of the visual evoked potentials were suppressed by R 5135 and the primary potential (N1) facilitated, virtually reducing the visual evoked potential to the form of an evoked spike. Pretreatment with the anticonvulsant GABAergic drugs gamma-acetylenic GABA (GAG) (100 mg/kg), sodium valproate (VPA) (400 mg/kg) and diazepam (5 mg/kg) suppressed the motor components of seizure activity, producing severe ataxia, but not the electrographic manifestation of seizure activity. Neither gamma-acetylenic GABA nor valproate significantly altered the latency to onset of spiking, although all three drugs did significantly reduce the frequency of discharges. Diazepam was the only anticonvulsant tested which completely suppressed spike activity in 3 of 5 rats. Moreover, R 5135 was found to antagonize diazepam, but not valproate induced suppression of secondary components of the visual evoked potential, suggesting that diazepam and R 5135 may compete for the same receptor.
D000200:Action Potentials / Q000187:drug effects; D000731:Androstanes / Q000494:pharmacology*; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D004569:Electroencephalography; D005074:Evoked Potentials, Visual / Q000187:drug effects; D006801:Humans; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects; D013260:Steroids, Heterocyclic / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000731:Androstanes; D001378:Azasteroids; D013260:Steroids, Heterocyclic; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D003975:Diazepam; C032061:RU 5135