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

采用相关的大鼠脑功能障碍模型，研究抗抑郁药、抗焦虑药和抗痴呆药的作用机制。抗抑郁药选择性地抑制杀鼠作用。在嗅球切除(OB)大鼠中，下丘脑外侧(LH)、下丘脑腹内侧部(VMH)、乳头体(MB)和杏仁内侧核(AME)去甲肾上腺素(NA)含量增加，去甲肾上腺素(NA)周转减少，5-羟色胺(5-HT)周转减少。在中脑损毁大鼠，5-羟色胺及其代谢产物显著降低，而黄体生成素和中缝大核的去甲肾上腺素含量显著增加，与杀鼠剂的发展相一致。在给予杀人剂的伏隔核(ACC)大鼠，LH、VMH和MB的NA含量显著增加，LH的5-羟色胺含量降低，MB的5-羟色胺周转率降低。结论：1.用抗抑郁药抑制的杀鼠剂可使杀鼠大鼠脑内单胺类物质的上述变化正常化。神经肽Y(NPY)可增强去卵巢大鼠AME微量注射NA的抗尿毒作用。在表现为杀人剂的OB大鼠中，LH、VMH和杏仁核的NPY含量显著增加。用抗抑郁药抑制杀人剂后，NPY的升高降至正常水平。在给予杀人剂的大鼠中，OB大鼠杏仁核和中缝大鼠下丘脑中5-HT2受体的数量显著增加，而5-HT1受体的数量不明显。去卵巢大鼠黄体生成素(Lh)和肾上腺皮质激素(VMH)中的NAr&lt；α&Gt；2受体减少。中央杏仁核(ACE)和MB是苯二氮类药物(BDZ)抗冲突作用的重要部位，但BDZ的作用机制不同。BDZ受体亚型在ACE和MB中的分布也不同。提供了相应的痴呆模型，并建立了定量测定记忆缺陷的有效方法，为抗痴呆药物的评价提供了依据。

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.