EFFECTS OF CHLORPROMAZINE ON THE N-METHYL-D-ASPARTATE DEPENDENT MECHANISMS OF LONG-TERM POST-TETANIC POTENTIATION FOR UNDERSTANDING OF MENTAL DISORDERS

DOI: https://doi.org/None

A.A. Mokrushin I.P. Pavlov Institute of Physiology, Nab. Makarova, 6, Saint-Petersburg, 199034, Russian Federation

Introduction. Clinical observations have revealed that the treatment of schizophrenia with the use of chlorpromazine (CPZ) impairs cognitive processes. Whether it is possible to eliminate these side effects of CPZ? The aim of the study. The aim of our study was to investigate the N-methyl-D aspartate (NMDA)-dependent non-associative form of learning as long-term potentiation (LTP) under the action CPZ, as well as eliminating its negative effects on this type of learning. Methods. Experiments carried out on surviving brain slices of the olfactory cortex of Wistar rats. We used electrophysiological techniques for extracellular brain slice recordings to investigate CPZ effects on learning processes in the model of LTP by measuring the activity of glutamate receptors (NMDARs). Results. Application of CPZ (10-5 M) on brain slices inhibited the development of LTP but enhanced long-term depression. These findings show that CPZ impaired the development of cognitive processes. In order to improve the cognitive functions under the action of CPZ we hypothesized that this antipsychotic negatively affects on the NMDARs. Slices were pretreated by ammonium chloride (NH4Cl, 20 mM) which is commonly recognized as fast and efficient lysosomal inhibitor. Pretreatment of slices NH4Cl and subsequent action of CPZ protected the development of LTP. Conclusion. Thus, the use of lysosomal inhibitor NH4Cl eliminates side effects of CPZ on cognitive processes.
Keywords: 
chlorpromazine, brain slices, long-term potentiation

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