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社会隔离对大鼠脑儿茶酚胺及强迫游泳的影响:抗抑郁治疗的预防作用

Effects of social isolation on brain catecholamines and forced swimming in rats: prevention by antidepressant treatment.

作者信息

Heritch A J, Henderson K, Westfall T C

机构信息

Department of Pharmacology, St. Louis University School of Medicine, MO 63104.

出版信息

J Psychiatr Res. 1990;24(3):251-8. doi: 10.1016/0022-3956(90)90014-h.

Abstract

Post-weaning rats were housed alone or in groups for a period of 4 or 8 weeks. A portion of the animals received tricyclic antidepressant treatment, desipramine 20 mg/kg/day, during this period. Animals were then tested behaviorally by forced swimming. Isolation was associated with significantly longer durations of immobility during forced swimming. This was blocked by desipramine treatment. Desipramine treatment did not have a significant effect on the swimming durations of group-housed rats. Hindbrain and midbrain levels of catecholamines were subsequently measured and turnover rates estimated by administration of alpha-methyl-p-tyrosine or saline. Isolated rats had increased levels and decreased turnover of catecholamines. The increase in norepinephrine but not dopamine levels was blocked by desipramine, while antidepressant effects on turnover could not be tested with this method. Reduced social stimulation thus appears to be associated with reduced catecholamine release which may result in the accumulation of these transmitters in the central nervous system. Treatment with desipramine appeared essentially to compensate for reduced social stimulation, blocking isolation-induced noradrenergic neurochemical changes, while having few significant effects on control animals. This study may be helpful in furthering our understanding of how the interaction of organisms with their environment influence catecholamine systems and how antidepressants may act to restore function.

摘要

断奶后的大鼠单独饲养或分组饲养4周或8周。在此期间,一部分动物接受三环类抗抑郁药治疗,即地昔帕明20毫克/千克/天。然后通过强迫游泳对动物进行行为测试。隔离与强迫游泳期间显著更长的不动时间相关。地昔帕明治疗可阻断这种情况。地昔帕明治疗对群居大鼠的游泳时间没有显著影响。随后测量了后脑和中脑的儿茶酚胺水平,并通过给予α-甲基-p-酪氨酸或生理盐水来估计周转率。隔离的大鼠儿茶酚胺水平升高且周转率降低。去甲肾上腺素水平的升高而非多巴胺水平的升高被地昔帕明阻断,而用这种方法无法测试抗抑郁药对周转率的影响。因此,社交刺激减少似乎与儿茶酚胺释放减少有关,这可能导致这些神经递质在中枢神经系统中积累。地昔帕明治疗似乎基本上可以补偿社交刺激的减少,阻断隔离诱导的去甲肾上腺素能神经化学变化,而对对照动物几乎没有显著影响。这项研究可能有助于进一步理解生物体与其环境的相互作用如何影响儿茶酚胺系统,以及抗抑郁药可能如何发挥作用来恢复功能。

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