Epilepsy Research
Volume 23, Issue 1 , Pages 37-53, February 1996

Anticonvulsant drug effects on spontaneous thalamocortical rhythms in vitro: Valproic acid, clonazepam, and α-methyl-α-phenylsuccinimide

  • Yun-Fu Zhang

      Affiliations

    • Department of Neurology, Medical College of Virginia, Richmond, VA, USA
    • ,
  • John W. Gibbs III

      Affiliations

    • Department of Anatomy, Medical College of Virginia, Richmond, VA, USA
    • ,
  • Douglas A. Coulter

      Affiliations

    • Corresponding Author InformationCorresponding author. Department of Neurology, P.O. Box 980599, Medical College of Virginia, Richmond, VA 23298-0599, USA. Tel.: (804) 828-3392; fax: (804) 828-6373
    • Department of Neurology, Medical College of Virginia, Richmond, VA, USA
    • Department of Anatomy, Medical College of Virginia, Richmond, VA, USA
    • The MCV Comprehensive Epilepsy Institute of Virginia Commonwealth University, Richmond, VA, USA

Received 1 March 1995; accepted 24 August 1995.

Abstract 

Spontaneous thalamocortical epileptiform activity was elicited in rodent thalamocortical slices by a medium containing no added Mg2+. Multiple varieties of activity were generated in these slices, including simple thalamocortical burst complex (sTBC) activity that resembled the spike-wave discharges of generalized absence epilepsy, and complex thalamocortical burst complex (cTBC) activity that resembled generalized tonic-clonic seizure discharges. In a further pharmacological characterization of this activity, the effects of the broad-spectrum anticonvulsants valproic acid, α-methyl-α-phenylsuccinimide (the active metabolite of methsuximide) and clonazepam were studied. All three drugs were found to be effective in controlling both sTBC and cTBC activity when applied in clinically relevant concentration ranges. The effectiveness of valproic acid against spontaneous rhythms in vitro was not due to augmentation of GABAergic inhibition. No effect of valproic acid on GABA-activated chloride currents was evident in patch-clamp recordings of acutely isolated thalamic or cortical neurons.

The equivalent general clinical and experimental spectrum of action of broadly effective anticonvulsants provided an additional correlation between the clinical efficacy of anticonvulsant drugs and their effects against epileptiform discharges in rodent thalamocortical slices. This further validates spontaneous generalized low-Mg2+ thalamocortical activity as a potentially valuable in vitro model of the primary generalized epilepsies, in which the cellular mechanisms underlying generation and control of these seizure discharges can be studied.

Keywords:  Generalized absence epilepsy, Seizure, Spike-wave discharge, Generalized tonic-clonic seizure, Thalamus, Cortex, Nucleus reticularis thalami, Benzodiazepine, GABA, Patch clamp

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PII: 0920-1211(95)00080-1

Epilepsy Research
Volume 23, Issue 1 , Pages 37-53, February 1996

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