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Potential antidepressant role of low-dose naltrexone in a rat model of chronic unpredictable mild stress
Int J Clin Exp Med
April 2017
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Objectives: We aimed to investigate antidepressant effect of low-dose naltrexone (LDN) and to explore its potential mechanism of action using a rat model induced by chronic unpredictable mild stress (CUMS). Methods: The CUMS-induced rat model was established, and the antidepressant effect of LDN (0.1 mg/kg/day, given by intraperitoneal injection for 5 weeks) was investigated using sucrose preference test, open field test, forced swimming test, and novelty-induced hyponeophagia test. Moreover, the molecular biological changes including beta-endorphin (BEP), interleukin (IL)-1ß, 5-hydroxy-tryptamine (5-HT), corticosterone, monoamine neurotransmitter and brain derived neurotrophic factor (BDNF) were also identified. Results: Behavioral changes were observed following 5 weeks of CUMS, including decreased sucrose preference, reduced locomotor activity, increased immobility time and elevated latency of feeding. However, after LDN treatment, these behavioral changes were significantly improved. In addition, LDN could inversed reduced BEP level in hypophysis, 5-HT level and BDNF expression level in hippocampus caused by CUMS. Moreover, LDN also could inversed increased levels of IL-1ß and corticosterone induced by CUMS. Conclusion: The results suggest that LDN may have therapeutic actions on depression-like behavior induced by CUMS in rats by decreasing IL-1ß in spleen and hippocampus tissue and plasma corticosterone levels and up-regulating the BEP level in hypophysis tissue and plasma and the 5-HT, BDNF level in hippocampus tissue.
Keywords: Antidepressant effects, low-dose naltrexone, high-dose naltrexone, chronic unpredictable mild stress rat model of depression