Pharmacological modulation of cholinergic brain activity and its reflection in special EEG frequency ranges from various brain areas in the freely moving rat (Tele-Stereo-EEG).

摘要

Due to the electrochemical nature of the communication structure of the brain an intimate relationship between neurotransmitter activity on one side and field potentials (EEG) on the other side can be suspected. In order to learn more about this relationship pharmacological manipulation of the cholinergic transmitter system by means of agonistic and antagonistic receptor active drugs was used. Continuous recording of electrical activity from four selected brain areas (frontal cortex, hippocampus, striatum and reticular formation) in freely moving day-night converted Fisher rats was used (Tele-Stereo-EEG). Frequency analysis of telemetrically transmitted data and special definitions of frequency ranges were used to analyse the data from 45 min pre-drug and 180 min postdrug periods. Pharmacological modulation of brain activity by the selective nicotinic agonist metanicotine as well as the alpha 7 selective nicotinic antagonist methyllycaconitine revealed major changes in delta (1-4.5 Hz) and alpha2 (9-12.5 Hz) frequencies. In general blockade of the cholinergic system resulted in electrical power increases and activation in decreases. Unspecific modulation of cholinergic activity by using the cholinesterase inhibitors physostigmine, tacrine and galantamine led to alpha1 frequency (7-9.5 Hz) changes in addition to the delta and alpha2 changes. These three drugs produced a nearly identical pattern of frequency changes. Theta (4.75-6.75 Hz) and beta1 frequencies (12.75-18.5 Hz) changed to a lesser degree. A peculiar finding arose with respect to the effects of the antagonistic drugs scopolamine and biperiden since biperiden-besides the massive increase of delta and alpha1 power in common-induced a general decrease of alpha2 frequencies within all brain areas opposite to the effect of scopolamine. This special property of biperiden gives a plausible explanation for its efficacy in Parkinsonian patients since decreases of alpha2 waves in this model indicate enhancement of dopaminergic transmission [Dimpfel, W., Spuler, M., Koch, R., Schatton, W., 1987. Radioelectroencephalographic comparison of memantine with receptor-specific drugs acting on dopaminergic transmission in freely moving rats. Neuropsychobiology 18, 212-218]. Except for the effects of methyllycaconitine (p<10%) all results were statistically significant at least at the p<5% level. The results are best explained by assuming that electrical delta activity reflects cholinergic transmitter control followed by and closely linked to changes in dopaminergic transmission as indicated by additional concomitant changes in alpha2 electrical power.