Balance and Imbalance of Transsynaptic Neurotransmission as Conditions for Normal and Pathological Behaviour: Examples Only

Abstract

For hundreds and even thousands of years drugs have been used to alter psychic behaviour, and alcohol is only one example of a drug that is still being used today. Since the beginning of our century, however, researchers have been interested in the mechanism(s) of drug action. It became clear by the early observations of Pötzl and Hess at the beginning of this century that glucose loading during melancholic phases led to changes in the response of depressed patients. Clinical, behavioural and biochemical studies after drug administration - including Freud’s first trials with cocaine — led to a break-through in biochemically oriented brain research. It became evident that rauwolfia serpentina improved psychotic behaviour and decreased blood pressure by releasing biogenic amines and emptying their specific storage sites (Carlsson 1959; Brodie and Shore 1957). This loss of biogenic amines caused depressive mood in about 10% of patients with hypertension. Generation of hypotheses that depression is caused by the loss of serotonin, noradrenaline and/or dopamine gave a first biochemical approach to the pathophysiology of psychiatric disturbances. On the other hand, research into the mechanism of action of reserpine showed its cataleptogenic effects in animal studies. This motor deficiency could be antagonized by the precursor amino acid of dopamine, L-dopa (Carlsson 1959). Later a loss of dopamine could be demonstrated in the nigrostriatal system of Parkinson’s disease (Ehringer and Hornykiewicz 1960). As a consequence of all these studies, L-dopa therapy was introduced by Birkmayer and Hornykiewicz (1961) and is nowadays a therapeutic standard for treatment of Parkinson disease.