The roles of central neurotransmitters in the mechanism of action of psychotropic drugs.

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The mechanisms of action of antidepressants, anxiolytics and antidementia drugs were investigated by using relevant models of brain dysfunction in rats.1. Muricide of the rat is selectively suppressed by antidepressants. In olfactory bulbectomized (OB) rats exhibiting muricide, noradrenaline (NA) content increased and NA turnover decreased in the lateral hypothalamus (LH), ventromedial hypothalamus (VMH), mammillary body (MB) and medial amygdala (AME), and serotonin (5-HT) turnover also decreased in LH and MB. In midbrain raphe-lesioned (Raphe) rats, 5-HT and its metabolites markedly decreased, but NA content in LH and VMH significantly increased, in accordance with the development of muricide. In nucleus accumbens-lesiond (Acc) rats exhibiting muricide, NA content significantly increased in LH, VMH and MB, 5-HT content decreased in LH and 5-HT turnover also decreased in MB. All these changes of brain monoamines in muricidal rats were mormalized with muricide suppressed by antidepressants.2. The antimuricide effect of NA microinjected into AME of OB rats was potentiated by neuropeptide Y (NPY). In OB rats exhibiting muricide, NPY content significantly increased in LH, VMH and the amygdala. This increase of NPY was reduced to the normal level with muricide inhibited by antideppressants.3. In the rats exhibiting muricide, the number of 5-HT_2 receptor but not of 5-HT_1 receptor significantly increased in the amygdala in OB rats and in the hypothalamus in Raphe rats. NAergic <alpha>2 receptors decreased in LH and VMH in OB rats.4. The central amygdala (ACE) and MB are the important sites of anticonflict action of benzodiazepines (BDZ), but the mechanism of action of BDZ was different in ACE and MB. The distribution of BDZ receptor subtypes was also different between ACE and MB.5. Relevant dementia models were provided and useful methods to quantitatively measure memory deficits were establishedfor evaluatiang antidementia drugs in rats.