Abstract

Whether benzodiazepines (BZDs) have beneficial effects on the progress of chronic stress-induced impairment of hippocampal structural plasticity and major depression is uncertain. The present study designed four preclinical experiments to determine the effects of BZDs using chronic unpredictable stress model. In Experiment 1, several time course studies on behavior and hippocampus response to stress were conducted using the forced swim and tail suspension tests (FST and TST) as well as hippocampal structural plasticity markers. Chronic stress induced depression-like behavior in the FST and TST as well as decreased hippocampal structural plasticity that returned to normal within 3 wk. In Experiment 2, mice received p.o. administration of three diazepam dosages prior to each variate stress session for 4 wk. This treatment significantly antagonized the elevation of stress-induced corticosterone levels. Only low- (0.5mg/kg) and medium-dose (1mg/kg) diazepam blocked the detrimental effects of chronic stress. In Experiment 3, after 7 wk of stress sessions, daily p.o. diazepam administration during 1 wk recovery phase dose-dependently accelerated the recovery of stressed mice. In Experiment 4, 1 wk diazepam administration to control mice enhanced significantly hippocampal structural plasticity and induced an antidepressant-like behavioral effect, whereas 4 wk diazepam administration produced opposite effects. Hence, diazepam can slow the progress of chronic stress-induced detrimental consequences by normalizing glucocorticoid hormones. Considering the adverse effect of long-term diazepam administration on hippocampal plasticity, the preventive effects of diazepam may depend on the proper dose. Short-term diazepam treatment enhances hippocampal structural plasticity and is beneficial to recovery following chronic stress.

Links

Publisher Full Text

Authors

Zhao Y, Wang Z, Dai J, Chen L, Huang Y, Zhan Z

Institution

Key Laboratory of Brain Research, Basic Medical College, Nanjing University of Traditional Chinese Medicine, Nanjing, China. zhaoyunan-js@163.com

Source

Behavioural brain research 228:2 2012 Mar 17 pg 339-50

MeSH

Analysis of Variance
Animals
Anti-Anxiety Agents
Brain-Derived Neurotrophic Factor
Corticosterone
Depression
Diazepam
Disease Models, Animal
Gene Expression Regulation
Hindlimb Suspension
Hippocampus
Male
Mice
Mice, Inbred C57BL
Neuronal Plasticity
Neurons
Stress, Psychological
Swimming
Synaptophysin
Time Factors

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22198054