Chronic antidepressant medication attenuates dexamethasone-induced neuronal death and sublethal neuronal damage in the hippocampus and striatum

被引:66
作者
Haynes, LE
Barber, D
Mitchell, IJ
机构
[1] Univ Nottingham, Queens Med Ctr, Sch Med, Nottingham NG7 2UH, England
[2] Univ Birmingham, Dept Psychol, Birmingham B15 2TT, W Midlands, England
关键词
caudate; SSRI; monoamine oxidase inhibitor; tricyclic; BDNF; MAP-2;
D O I
10.1016/j.brainres.2004.05.117
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Dexamethasone, a synthetic corticosteroid, which can induce a range of mood disorders including depression and affective psychosis, is toxic to specific hippocampal and striatal neuronal populations. Chronic administration of antidepressants can induce neuroprotective effects, potentially by raising cellular levels of brain-derived neurotrophic factor (BDNF). We accordingly tested the hypothesis that chronic pretreatment of rats (Sprague-Dawley, male) with antidepressants would attenuate dexamethasone-induced neuronal damage as revealed by reductions in the level of neuronal death and in sublethal neuronal damage shown by the increase in the number of MAP-2 immunoreactive neurons. In support of this hypothesis, we demonstrate that chronic treatment with a range of antidepressants prior to dexamethasone administration (0.7 mg/kg, i.p.) attenuated the levels of neuronal death and loss of MAP-2 immunoreactivity in both the hippocampus and striatum. The antidepressants used were: desipramine (8 mg/kg, i.p., tricyclic), fluoxetine (8 mg/kg, i.p., selective serotonin reuptake inhibitor) and tranylcypromine (10 mg/kg, i.p., monoamine oxidase inhibitor) with each drug being injected once per day for 10 days. In contrast, acute injection of none of the antidepressants exerted a protective effect from dexamethasone-associated neuronal damage. Similarly, injection of neither cocaine nor chlordiazepoxide (benzodiazepine) exerted protective effects when injected either chronically or acutely. The observed protection from dexamethasone-induced neuronal damage is in keeping with the potential of chronic antidepressant medication to increase BDNF levels. The potential for dexamethasone to induce disorders of mood by damaging specific neuronal populations in the hippocampus and dorsomedial striatum is discussed. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:157 / 167
页数:11
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