Tachykinins may modify spontaneous epileptiform activity in the rat entorhinal cortex in vitro by activating GABAergic inhibition
Section snippets
Experimental procedures
Most experiments were performed on brain slices prepared from male Wistar rats (120–150 g; Bantin & Kingman, Hull, U.K.). Slices containing the EC, hippocampus and temporal cortex were prepared as described previously.[21]In some experiments coronal slices containing anterior cingulate cortex were also examined. Animals were anaesthetized with a mixture of ketamine (120 mg/kg) and xylazine (8 mg/kg) administered i.m., and decapitated. The brain was removed and submerged in chilled (4–5°C)
Membrane effects
The effects of bath application of SP were tested on 115 principle neurons (as opposed to interneurons) in the MEC, 61 in layer V and 54 in layer II. SP had little effect on most neurons in either layer, even at very high concentrations (up to 10 μM). Membrane potential and input resistance (mean±S.E.M.) in layer V neurons just before application of SP (n=51) were −72.7±0.9 mV and 35.8±6.5 MΩ, respectively. During application of the peptide the respective values were −71.8±0.8 mV and 35.2±6.6 MΩ.
Discussion
In summary, we have found that the vast majority of principle neurons in the rat MEC are largely unaffected by SP. This lack of effect was surprising in view of the powerful excitatory actions of SP on cortical neurons seen in vivo,1, 23, 24, 25, 26, 29, 40and considering data showing a high density of binding sites for SP in the EC.6, 9, 27, 31A similar lack of effect in slices of rat anterior cingulate cortex suggested that regional differences are unlikely to be a factor. The present results
Conclusion
Whether our results in slices have any relevance for epileptogenesis or anti-epileptic effects in man can only be the subject of conjecture at present. However, NK1-receptors are phylogenetically preserved in higher species including man[8]and it would be worthwhile, therefore to investigate the use of agonists at these receptors as anticonvulsants.
Acknowledgements
We are grateful to the Wellcome Trust, the Royal Society and Glaxo Group Research for financial support for this study.
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Present Address: Merck Sharpe and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, U.K.