Antidepressant effects of resveratrol in an animal model of depression

Abstract

Resveratrol (3,4’,5-trihydroxy-trans-stilbene) is a natural non-flavonoid polyphenol antioxidant extracted from red grapes in the processing of wine. Initially it was studied for its potential as anticancer drug, and later was found to reduce cardiovascular disease. More recently resveratrol was shown to alleviate depressive-like symptoms induced by stress or other means in mice and rats. The major purpose of this study was to investigate whether resveratrol would manifest an antidepressant effect in Wistar-Kyoto (WKY) rats, a putative and non-induced animal model of depression, and whether this effect might be associated with an increase in hippocampal and frontal cortical brain-derived neurotrophic factor (BDNF), a protein implicated in chronic effects of many antidepressants. Adult male WKY rats were injected with two doses of resveratrol (10 and 40 mg/kg, i.p.) and their behavior in the open field locomotor activity (LMA), forced swim test (FST: a measure of helplessness), and sucrose preference test (SPT: a measure of anhedonia) was evaluated after a single acute injection or following 7 days of daily treatment. Both acute and chronic administration of resveratrol resulted in a dose-dependent decrease in FST. However, only chronic resveratrol resulted in dose-dependent increase in sucrose consumption. LMA was not affected by any treatment. Parallel to the observed behavioral effects the level of hippocampal, but not frontal cortical, BDNF was also dose-dependently elevated after chronic resveratrol administration. These findings indicate an antidepressant-like effect of resveratrol in an animal model of depression possibly via activation of hippocampal BDNF, and suggest therapeutic potential of resveratrol in at least a subpopulation of depressed patients.

Resveratrol Reverses the Synaptic Plasticity Deficits in a Chronic Cerebral Hypoperfusion Rat Model

“…24 Meanwhile, resveratrol had also been used in the treatment of depression by the activation of brain-derived neurotrophic factor (BDNF) signal. 25 In a previous study, it is shown that resveratrol treatment prevented both spatial working and reference memory impairments in CCH rats. 26 In this study, we extend the possible mechanism of resveratrol prevention on synaptic disorder in dendritic spines in CCH rats.…”

Anti-tumor effects and cellular mechanisms of resveratrol

“…It also has a cardio-protective effect (6) that regular moderate consumption of red wine confers less risk of cardiovascular diseases due to its relatively high resveratrol concentration (0.1-14.3 mg/L), widely known as the "French Paradox" (7). There are also other effects, which include phytoestrogen activity (8), neuroprotective activity (9), and antidepressant activity (10).…”

The pharmacology of resveratrol in animals and humans

“…RSV treatment improved the helplessness symptom as judged by reducing the duration of immobility in the tail suspension or forced swimming tests in rats [264] and mice [265,266]. Also, under chronic stress conditions, an increase in immobility time in both forced swim and tail suspension tests [267], a decrease in sucrose preference [268], the learned helplessness using the shuttle box method [268], and an increase in adrenal gland/body weight [268], were reversed by RSV treatment in rats.…”

“…RSV induced brain-derived neurotrophic factor (BDNF) levels in the hippocampus of unstressed rats [264] and mice [269], as well as reversed the reduced expression of BDNF in the prefrontal cortex and hippocampus of chronic mild stress-exposed rats [270]. In addition, the reduced phosphorylation levels of cAMP response elementbinding protein (CREB) and ERK, which is involved in learning, memory, and neuroplasticity, were normalized by RSV in stressed rats [270].…”