Preventive effects of blueberry extract on behavioral and biochemical dysfunctions in rats submitted to a model of manic behavior induced by ketamine

Abstract

The aim of the present study was to evaluate the protective effects of blueberry extract on oxidative stress and inflammatory parameters in a model of mania induced by ketamine administration in rats. Male rats were pretreated with blueberry extract (200mg/kg, once a day for 14days), lithium chloride (45mg/kg, mood stabilizer used as a positive control, twice a day for 14days), or vehicle. Between the 8th and 14th days, rats also received an injection of ketamine (25mg/kg) or vehicle. In the 15th day, thirty minutes after ketamine administration the hyperlocomotion of the animals was assessed in the open - field apparatus. Immediately after the behavioral analysis brain and blood were collected for biochemical determinations. ketamine treatment induced hyperlocomotion and oxidative damage in cerebral cortex, hippocampus and striatum such as an increase in lipid peroxidation and a decrease in the antioxidant enzymes activities (superoxide dismutase, catalase e glutatione peroxidase). Ketamine administration also increased the IL-6 levels in serum in rats. Pretreatment of rats with blueberry extract or lithium prevented the hyperlocomotion, pro - oxidant effects and inflammation induced by ketamine. Our findings suggest that blueberry consumption has a neuroprotective potential against behavioral and biochemical dysfunctions induced in a preclinical model that mimic some aspects of the manic behavior.

Health promoting properties of blueberries: a review

“…In fact, the neurotoxic effects of kainic acid, in rats, have been reported to be reduced after consumption of blueberry, which ameliorated the exacerbated kainic acid induced inflammatory response in the hippocampus (Shukitt-Hale et al 2008). In fact, blueberry consumption (either directly or through anthocyanin rich extracts) has been demonstrated to have an in vitro neuroprotective effect against damage induced by an array of neurotoxic agents (such as trimethyltin and ketamine), while also exhibiting some in vivo effects in protecting and, in some cases, even enhancing the learning and memory capabilities of mice (Jo et al 2015;Andres-Lacueva et al 2005;Debom et al 2016). An effect that Krikorian et al (2010) showed to be expanded to humans, as the consumption of blueberries by older adults improved memory capabilities, which may be explained by an increase in synaptic plasticity resulting from a modulation of the microglia phenotype towards a more favorable M2 phenotype and an improvement of the microglia-neuron crosstalk through the increase of the expression of CX3CR1 receptor (an element of the CXCR1/CX3CL1 axis that connects microglia and neuron cells) (Meireles et al 2016).…”

Gallic acid protects cerebral cortex, hippocampus, and striatum against oxidative damage and cholinergic dysfunction in an experimental model of manic‐like behavior: Comparison with lithium effects

“…In order to follow the principles of the Three Rs (replacement, reduction, and refinement) in relation to animal experimentation, this study did not evaluated the per se effect of lithium. Previous studies using the same animal model of mania showed that lithium per se did not induce changes in behavior and brain oxidative stress parameters (Debom et al., 2016).…”

“…Ketamine alters glutamatergic neurotransmission because it acts as a noncompetitive antagonist of N‐methyl‐D‐aspartate receptor, inducing changes in the rat brain similar to those described in BD patients (Ghedim et al., 2012). In addition, ketamine increases the locomotor activity in animals, and this effect of ketamine is attenuated by lithium treatment (Debom et al., 2016). Our findings showed that ketamine induces manic‐like behavior in rats that was evaluated using the open field test.…”

“…Thirty minutes later, locomotor activity was assessed in an open field apparatus (Figure 1). The dose of gallic acid and ketamine used were based on previous studies (Debom et al., 2016; Mansouri et al., 2013). In order to follow the principles of the Three Rs (replacement, reduction, and refinement) in relation to animal experimentation, this study did not evaluated the per se effect of lithium.…”

“…Ketamine is a dissociative anesthetic that acts as a noncompetitive antagonist of the NMDA glutamate receptor. Thus, at non‐anesthetic doses, ketamine administration induces manic‐like behavior in rats, as demonstrated by hyperlocomotion (Chaves et al., 2020; Debom et al., 2016; Ghedim et al., 2012; Spohr et al., 2019).…”