Abstract
Schizophrenia is a mental illness and its pharmacological treatment consists in the administration of antipsychotics like haloperidol. However, haloperidol often causes extrapyramidal motor disorders such as tardive dyskinesia (TD). So far, there is no effective treatment against TD and alternatives for it have been sought. Isoflafones have been studied as neuroprotector and inhibitor of monoamine oxidase enzyme. Thus, the objective is to evaluate the possible protective effect of isoflavones against the induction of involuntary movements induced by haloperidol in an animal model. Male Wistar rats were treated with haloperidol (1mg/kg/day) and/or isoflavones (80mg/kg) for 28 days. Rats were submitted to behavioral evaluation to quantify vacuous chewing movements (VCM) and locomotor activity. In addition, the levels of pro-inflammatory cytokines were measured in the striatum. Haloperidol treatment reduced the locomotor activity and increased the number of VCM in rats. Co-treatment with isoflavones was able to reverse hypolocomotion and reduce the number of VCM. Besides, haloperidol caused significant increase in the proinflammatory cytokines (interleukin-1β:IL-1β, tumor necrosis factor-α: TNF-α and IL-6 and the co-treatment with isoflavones was able to reduce the levels of IL-1β and TNF-α, but not IL-6. It is believed that the beneficial effect found with this alternative treatment is related to its anti-inflammatory potential and to the action on estrogen receptors (based on scientific literature findings). Finally, further studies are needed to elucidate the mechanisms of isoflavones in reducing motor disorders induced by antipsychotics.
Highlights
Schizophrenia is a serious mental illness, with a prevalence of approximately 1% in the world population (Ijaz et al 2018)
To evaluate the effect of the isoflavones treatment to reducing movement disorders induced by haloperidol, the number of VCM at 29 day was quantified for each animal
This study aimed to investigate the possible protective effect of isoflavones against involuntary movements induced by haloperidol in rats and the role of proinflammatory cytokines in this process
Summary
Schizophrenia is a serious mental illness, with a prevalence of approximately 1% in the world population (Ijaz et al 2018). The etiology of the disease is still uncertain, the hypothesis of dopaminergic hyperfunction is one of the most accepted (Nardi et al 2015). The pharmacological treatment of schizophrenia consists in the administration of antipsychotics, which are divided into first generation (eg, haloperidol), second generation (eg: risperidone) and more recently third generation (aripriprazole) (Brown et al 2012). One of the most potent and most used antipsychotics, haloperidol, acts by preferentially antagonizing the dopamine receptor of subtype D2, reducing dopamine levels in different dopaminergic pathways and being effective mainly against positive symptoms of schizophrenia, such as hallucinations. Treatment with haloperidol often causes extrapyramidal motor disorders (parkinsonism, akathisia, dystonia and tardive dyskinesia) (Amato et al 2016)
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