Reversal of haloperidol-induced orofacial dyskinesia and neuroinflammation by isoflavones

Abstract

Schizophrenia is a serious mental illness, and its pharmacological treatment consists in the administration of antipsychotics, such as haloperidol. However, treatment with haloperidol often causes extrapyramidal motor disorders such as tardive dyskinesia (TD). TD is a movement disorder characterized by involuntary movements, which can be studied in animals. So far, there is no effective treatment for TD and alternatives have been sought. Thus, the objective was to evaluate the possible protective effect of iso avones against the induction of involuntary movements induced by haloperidol in an animal model. Male Wistars rats were treated with haloperidol (1 mg/ kg/day) and/or iso avones (80 mg/kg) for 28 days. Rats were submitted to behavioral evaluation to quantify vacuous chewing movements (VCM) and the locomotor activity. In addition, the levels of pro-in ammatory cytokines were measured in the striatum. Haloperidol treatment reduced the locomotor activity and increased the number of VCM in rats. Co-treatment with iso avones was able to reverse hypolocomotion and reduce the number of VCM to the levels of the control group. Besides, haloperidol caused signi cant increase in the proin ammatory cytokines (interleukin-1β:IL-1β, tumor necrosis factor-α:TNF-a and IL-6 and the cotreatment with iso avones was able to reduce the levels of IL-1β and TNF-α, but not IL-6. It is believed that the bene cial effect found with this treatment is related to their anti-in ammatory potential and also to the action on estrogen receptors (based on ndings in the scienti c literature). Finally, further studies are needed to elucidate the mechanisms of iso avones in reducing motor disorders induced by antipsychotic.

NLRP3/Caspase-1-Mediated Pyroptosis of Astrocytes Induced by Antipsychotics Is Inhibited by a Histamine H1 Receptor-Selective Agonist

“…Our previous study has reported that in both cultured astrocytes and the rat prefrontal cortex, olanzapine increased the expression of IL-1β ( Li et al, 2021c ). Haloperidol increased IL-β in the rat brain ( Sonego et al, 2021 ; Mezzomo et al, 2022 ). These findings suggest that antipsychotics such as olanzapine and haloperidol might significantly affect the NLRP3/caspase-1 signaling, leading to IL-1β production and astrocyte death.…”

Empagliflozin Protects against Haloperidol Experimentally-Induced Ovarian Toxicity

“…EMPA is an antidiabetic drug that inhibits SGLT2, which offers clinically meaningful protection in type 2 diabetic individuals [ 25 ]. Attenuation of oxidative stress, inflammation, and apoptosis are considered some of the postulated mechanisms of EMPA effects in tissue protection [ 26 , 27 ].…”

Putative role of immune reactions in the mechanism of tardive dyskinesia

“…Increased (in comparison to control animals who were only exposed to the vehiculum used) striatal levels of IL-1β were invariably found in rodent models of haloperidol-induced orofacial dyskinesia ( Grover et al, 2013 ; Peroza et al, 2016 ; Thakur et al, 2015 ; Datta et al, 2016 ; Sonego et al, 2018 , 2021 ; Mezzomo et al, 2022 ). Both dyskinesia and IL-1β levels were reduced when the animals received concurrent antioxidant treatment.…”