Anticonvulsant, but Not Antiepileptic, Action of Valproate on Audiogenic Seizures in Metaphit–treated Rats

Abstract

1. The blocking effects of valproate (2-propylpentanoic acid), a standard anti-epileptic drug, on metaphit (1-[1-(3-isothiocyanatophenyl)-cyclohexyl]-piperidine)-induced audiogenic seizures as a model of generalized, reflex audiogenic epilepsy in adult Wistar male rats were studied. 2. Rats were stimulated using an electric bell (100 +/- 3 dB, 5-8 kHz, 60 s) 60 min after i.p. metaphit (10 mg/kg) injection and afterwards at hourly intervals. For power spectra and electroencephalograph (EEG) recordings, three gold-plated screws were implanted into the skull. Different doses of valproate (50, 75 and 100 mg/kg) were injected i.p. into rats with fully developed metaphit seizures after the eighth audiogenic testing. 3. In metaphit-treated animals, the EEG appeared as polyspikes, spike-wave complexes and sleep-like patterns, whereas the power spectra were increased compared with the corresponding controls. 4. Valproate reduced the incidence and intensity of convulsions and prolonged the duration of the latency period in a dose-dependent manner 4 h after administration. 5. The ED(50) of valproate in the first hour after injection was 63.19 mg/kg (95% confidence interval 51.37-77.71 mg/kg). 6. None of the doses of valproate applied eliminated the EEG signs of metaphit-provoked epileptiform activity. 7. Taken together, these results suggest that all doses of valproate examined acted to suppresse behavioural but not epileptic EEG spiking activity in metaphit-induced seizures.

The effect of intracerebroventricular administration of orexin receptor type 2 antagonist on pentylenetetrazol-induced kindled seizures and anxiety in rats

“…However, the drug did not exhibit significant effect on electrocortical activity. So, they concluded that valproate is an anticonvulsant rather than antiepileptic drug [ 62 ]. By comparison, it may be suggested that TCS OX2 29 had a higher potency than valproate.…”

Modulation of Epileptic Activity in Rats: Focus on Sleep, Physical Exercise and Nitric Oxide–mediated Neurotransmission in a Model of Homocysteine Thiolactone–induced Seizures

“…Modelling the epileptic activity in animals involves two main approaches: administering different chemical compounds and electrical stimulation kindling. In our Laboratory for Neurophysiology, different animal models have been developed, including metaphit audiogenic seizures (18)(19)(20)(21) and lindane- (22)(23)(24) and homocysteine thiolactoneinduced seizures (11). In addition to these models, the other commonly used experimental epilepsy models are those induced by factors such as N-methyl-D-aspartate (NMDA), pentylenetetrazol, pilocarpine, kainic acid, and 4-aminopyridine amygdala kindling (for review see 4).…”

Neural pathways underlying the interplay between emotional experience and behavior, from old theories to modern insight

“…The generative and regulatory processes of both systems (bottom-up and top-down) are closely interdependent and overlap in neural processes that are in constant interaction. By experimental research on animal models and using the method of neurophysiological lesions, specific cortical and subcortical neural networks have been identified as a biological substrate for emotions [33,50,51]. Emotion regulation and control arise as a complex process in a network of neural groups that mediate cognitive, emotional and behavioral functions (the prefrontal cortex, limbic, and temporal regions).…”