Study on pathological mechanisms of temporal lobe epilepsy and psychosis through kindling effect

Abstract 

This paper describes the creative research works by Prof Mitsumoto Sato. Prof Sato considered kindling effect, which was discovered by Goddard in 1969, as a good model of epilepsy, psychosis and engram of memory. He first carried out amygdala kindling effect researches in Vancouver. After his return to Japan, Prof Sato continued to study on hippocampus kindling and temporal lobe cortex kindling and their transference phenomenon. He reported on the formation of kindling effect, its development time frame, distinct stage-wise progression, tendency to return to partial seizure, recurrent spontaneous convulsive seizures similar to the kindled one, relationship with limbic-brain stem connections and transference phenomenon. Later Prof Sato studied so-called dopamine kindling, but pointed out the necessity to differentiate this phenomenon from kindling and called this as reverse tolerance phenomenon. Prof Sato found that repeated use of central stimulant generate psychosis similar to schizophrenia and reported that chronic intake of catecholaminergic agents can cause long-term change of the brain with cross sensitization, and clarified that reverse tolerance phenomenon can be triggered by other kind of catechoraminergic agents and that dopamine receptor blockers can suppress this phenomenon. Together with additional clinical studies on stimulant-induced psychosis, Prof Sato found that reverse tolerance phenomenon is a new experimental tool for investigating vulnerability of psychoses including schizophrenia. Later Prof Sato led the renaming of schizophrenia movement in Japan. This tells best the integrated interest as scientist and humanitarian clinician to provide help to people who suffer from psychosis.

Keywords: Kindling, Temporal lobe epilepsy, Engram, Reverse tolerance, Vulnerability model