Murray, Anthony Charles; (1992) Pharmacological evaluation of epileptiform models in rat cerebral cortex slices. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

The addition of bicuculline to, or the removal of Mg++ from, the bathing medium enabled slices of rat cerebral cortex reliably to show epileptiform activity at room temperature. The Mg++-free model, but not the bicuculline model, was also reliable at 35°C. Other convulsants evaluated were unreliable and these models were not developed further. The effects of taurine, glycine and D-serine on event frequency and event shape (amplitude, afterdischarge number and duration) were investigated in the Mg++-free model at 35°C. All three amino acids caused increases in event frequency. Higher taurine concentrations caused a reversal of the initial increase. Taurine had no consistent effect on event shape. At high concentrations, glycine and D-serine caused a reduction in afterdischarge number. Bicuculline and strychnine were of limited use in determining taurine's mode of action since they both caused increases in event frequency. The glycine-mediated increase was antagonized by HA-966 whereas the taurine response was unaffected. At low concentrations, pentobarbitone, phenobarbitone, quinalbarbitone, butobarbitone, alphaxalone and phenytoin, caused an increase in the event frequency in the Mg++-free model at 35°C, which was not seen at room temperature. At higher concentrations all agents, except phenytoin, caused a reduction in both event frequency and, together with phenytoin, a reduction in afterdischarge number. Pentobarbitone, phenobarbitone and alphaxalone also reduced event frequency and afterdischarge number in the bicuculline model. Greater concentrations were needed to reduce event frequency than afterdischarge number in both models. This may indicate that different mechanisms underlie the two phenomena. In the presence of taurine, lesser concentrations of pentobarbitone and phenobarbitone were needed to reduce event frequency in the Mg++-free model at 35°C. Greater concentrations were required in the bicuculline model. This phenomenon may be temperature-related. The data are interpreted in terms of the established interactions of these substances with excitatory/inhibitory amino acid transmitter systems.

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