Effect of compounds modulating amino acid neurotransmission on the development and control of bicuculline-induced epileptogenic spiking in the rat.
Dose-related EEG spiking was induced and monitored in urethane-anaesthetised rats by cortical superfusion of bicuculline methiodide, through a cortical cup incorporating recording electrodes. The total integrated spike voltage, total number of spikes as well as the average size of the spikes were monitored. Extracellular recording showed that each individual EEG spike coincided with the sudden, synchronous firing of a group of superficial cortical cells (layer II-III). gamma-Aminobutyric acid reduced both the size and frequency of the spikes, whilst muscimol and clonazepam mainly reduced the size of the spikes. (+/-) Baclofen reduced the frequency of the spikes, with no effect on their size. The NMDA receptor antagonists, AP5 and AP7 reduced spiking by attenuating size, with no effect on frequency. The NMDA channel blocker MK801 also reduced the size of the spikes but increased their frequency at large concentrations; increasing magnesium in the artificial CSF, from 1 to 10 mM, had a similar effect. Compounds believed to preferentially block non-NMDA receptors, GAMS and CNQX, reduced activity by mainly reducing the frequency of spikes. It is concluded that activation of non-NMDA and GABAB receptors are important for controlling the initiation of bicuculline-induced spikes and NMDA and GABAA receptors, for the control of their subsequent development.
Zia-Gharib
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Department of Pharmacology, University College London, England.
Webster
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RA
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage; D002540:Cerebral Cortex / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D018377:Neurotransmitter Agents; D001640:Bicuculline