Adell A, García-Marquez C, Armario A, Gelpí E
Departament de Neuroquímica, C.S.I.C., Barcelona, Spain.
Psychopharmacology (Berl). 1989;99(1):22-6. doi: 10.1007/BF00634447.
The effects of chronic clomipramine administration (15 mg/kg daily for 23 days) on changes in serotonin (5-hydroxytryptamine, 5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline (NA) induced by chronic stress have been studied in the rat brain. Chronic stress increased 5-HT in midbrain, pons and hippocampus, 5-HIAA in frontal cortex, midbrain, pons and hippocampus, and NA in midbrain and striatum. Chronic clomipramine significantly decreased the levels of 5-HT in most regions. In hypothalamus, hippocampus and perhaps in frontal cortex this effect possibly reflects decreased synthesis caused by an action on presynaptic 5-HT receptors. However, in midbrain, pons and striatum decreased 5-HT could not be attributed to a decrease in its synthesis since 5-HIAA also increased. This drug treatment also reduced NA in all regions except the striatum. Nevertheless, conclusions on NA synthesis or turnover cannot be drawn since only NA levels were measured. When administered concurrently, chronic clomipramine prevented the increases in 5-HT, 5-HIAA and NA produced by chronic stress. These results are in good accordance with previous findings showing that chronic antidepressant treatment also prevented behavioural disturbances induced by chronic stress.
研究了慢性给予氯米帕明（每天15mg/kg，持续23天）对大鼠脑中慢性应激诱导的血清素（5-羟色胺，5-HT）、5-羟吲哚乙酸（5-HIAA）和去甲肾上腺素（NA）变化的影响。慢性应激使中脑、脑桥和海马中的5-HT增加，额叶皮质、中脑、脑桥和海马中的5-HIAA增加，中脑和纹状体中的NA增加。慢性给予氯米帕明显著降低了大多数区域的5-HT水平。在下丘脑、海马以及可能在额叶皮质中，这种作用可能反映了对突触前5-HT受体的作用导致合成减少。然而，在中脑、脑桥和纹状体中，5-HT的降低不能归因于其合成减少，因为5-HIAA也增加了。这种药物治疗还降低了除纹状体以外所有区域的NA水平。然而，由于仅测量了NA水平，因此无法得出关于NA合成或周转的结论。当同时给药时，慢性给予氯米帕明可防止慢性应激引起的5-HT、5-HIAA和NA增加。这些结果与先前的研究结果一致，表明慢性抗抑郁治疗也可防止慢性应激引起的行为障碍。
