Antidepressant effects of moxidectin, an antiparasitic drug, in a rat model of depression.

Substantial data indicate that an imbalance in gut microbiome (GM), also referred to as dysbiosis, may play an important role in depression. Moreover, drugs that normalize GM can result in an antidepressant-like effect. It was reported recently that moxidectin (MOX), an antiparasitic drug commonly used in veterinary medicine, has a positive influence on microbiota implicated in mood regulation. We undertook this study to determine whether MOX would actually show antidepressant-like properties in an animal model of depression and whether it would affect the hippocampal and frontal cortex levels of brain-derived neurotrophic factor (BDNF) or tumor necrosis factor (TNF)-alpha, peptides that have been implicated in pathogenesis of depression and effectiveness of various antidepressants. Adult male Wistar-Kyoto rats, a putative animal model of depression, were treated with a single dose of MOX (2.5 mg/kg, i.p.) and their performance in the open field locomotor activity (OFLA) as well as in the forced swim test (FST) was evaluated at 24 h, one week and two weeks after the single injection. A separate group of rats were injected with 2.5 mg/kg MOX and sacrificed 24 h later for neurochemical evaluations. MOX resulted in a decrease in immobility score after 24 h, whereas OFLA was not affected. Concomitant with the 24 h behavioral effects, the levels of hippocampal and frontal cortical BDNF were significantly increased, whereas the levels of TNF-alpha in both these areas were significantly decreased. The decrease in immobility scores was still evident after one week, but not 2 weeks of rest. These results indicate long lasting antidepressant effects of a single MOX dose and suggest potential utility of this drug in treatment-resistant depression.