EFFECT OF ANTIDEPRESSANT DRUGS ON DEPLETION OF INTRANEURONAL BRAIN 5-HYDROXYTRYPTAMINE STORES CAUSED BY 4-METHYL-ALPHA-ETHYL-META-TYRAMINE

Mice were injected with 4-methyl-α-ethyl-meta-tyramine (two doses of 100 mg/kg i.p.). After 4 h the animals were killed and the brains analyzed for 5-hydroxytryptamine (5-HT) biochemically or examined under the fluorescence microscope after formaldehyde treatment. The amine caused more than 50 per cent depletion of 5-HT, probably by displacement. Pretreatment with antidepressant drugs of imipramine type largely prevented 5-HT depletion, probably by blocking the amine uptake mechanism of the cell membrane of 5-HT neurons. Tertiary amines, e.g. chlorimipramine, imipramine and amitriptyline, were more potent in this respect than the corresponding secondary amines, in contrast to previous observations on noradrenaline neurons. In rats similar observations were made (histochemical observations only). It is suggested that blockade of 5-HT re-uptake is involved in the mood-elevating action of tricyclic antidepressants, whereas blockade of noradrenaline re-uptake promotes drive in the depressed patient. © 1969.