Endogenous acetylcholine facilitates epileptogenesis in immature rat neocortex.

In the presence of the gamma-amino butyric acid-A (GABAA) antagonist bicuculline methiodide (50 microM), synchronous spontaneous and evoked potentials were recorded extracellularly from the deep layers of immature neocortex (postnatal days 10-31, P10-P31) in vitro. Addition of the anticholinesterase eserine (10 microM) depressed the amplitude (by 29.5+/-6.6%, n=13) and duration (by 26.3+/-4.7%, n=11) of the evoked field potentials in 13/19 slices (68%), and increased significantly the rates of occurrence of spontaneous epileptiform discharges or induced them in 9/19 slices (47%). All these effects were blocked by the muscarinic antagonist atropine (2.5 microM, n=3), suggesting that they were mediated by the activation of muscarinic receptors by endogenous acetylcholine. The cholinergic inhibitory effect is unlikely to terminate seizures, while the excitatory effect, could conceivably promote or aggravate their manifestation. In conclusion, these findings demonstrate that endogenous acetylcholine may contribute to epileptogenesis in immature neocortex.