L-Theanine Decreases Orofacial Dyskinesia Induced by Reserpine in Rats

Abstract

Reserpine (RES)-induced orofacial dyskinesia (OD) has been used as an animal model for human tardive dyskinesia (TD) for decades, due to its strong pathophysiological association with striatal oxidative stress and neural cytoarchitecture alteration. -Theanine (LT), one of the major amino acid components in green tea, has potent antioxidative, anti-inflammatory, and neuroprotective effects. In this study, we examined the potential protective effects of LT on RES-induced behavioral and neurochemical dysfunction in rats. RES treatment (1 mg/kg s.c., 3 injections 1 day apart) induced significant increases (p< 0.001) in the frequency of vacuous chewing movements (VCM), tongue protrusion (TP), as well as the duration of facial twitching (FT). LT treatment (100, 300 mg/kg orally for 14 days, starting 10 days before RES injection) was able to prevent most of the RES-induced OD. Moreover, LT treatment reduced the RES-induced lipid peroxidation (LPO) production, increased the antioxidation power and catecholamines in the striatum, and significantly reduced the levels of neuroinflammatory and apoptotic markers. Our results indicated that LT was able to counteract the increased oxidative damage, neurotransmitter deficiency, neuroinflammation, and apoptosis induced by RES, and these results have demonstrated the possible neuroprotective effects of LT against RES-induced OD, including antioxidation, neurochemical deficiency prevention, antineuroinflammation, and antiapoptosis. These findings, therefore, suggest a potential role for LT to have a clinically relevant therapeutic effect in delaying or treating human TD.

Green Tea, A Medicinal Food with Promising Neurological Benefits

“…human model for tardive dyskinesia. The result of l-theanine administration was in favor of antioxidant, anti-inflammatory, and anti-apoptosis features of this component [ 39 ]. Another investigation showed that l-theanine can decrease the amount of nitric oxide production and may act as an anti-inflammatory agent [ 40 ].…”

Genetic Factors Associated With Tardive Dyskinesia: From Pre-clinical Models to Clinical Studies

“…In most models, TD is induced by treatment with the FGA haloperidol, commonly prescribed in patients with schizophrenia ( Marder and Cannon 2019 ). Additionally, fluphenazine, one of the oldest antipsychotics ( Matar et al, 2018 ) and reserpine, an indole alkaloid used as antipsychotic and antihypertensive agent ( Soung et al, 2018 ) are used to induce TD in experimental animals as well. The phenotype of TD in animals is different in comparison to human beings since it presents with robust, seemingly purposeless chewing activity (so-called vacuous chewing movements or VCM), often fluctuating, and occurring in short bursts, occasionally associated with bruxism and tongue protrusions.…”

“…Animal experiments studied candidate pathways involved in TD development on the level of functional perturbations due to treatment with antipsychotics. Inflammation ( Bishnoi and Boparai 2012 ; Grover et al, 2013 ; Thakur et al, 2015 ; Datta et al, 2016 ; Peroza et al, 2016 ; Sonego et al, 2018 ; Soung et al, 2018 ; Wang et al, 2021a ) and oxidative stress defense ( Patil et al, 2012 ; Grover et al, 2013 ; Nade et al, 2013 ; Thakur et al, 2015 ; Wang et al, 2015 ; Datta et al, 2016 ; Schaffer et al, 2016 ; Samad and Haleem 2017 ; Dhingra et al, 2018 ; Sonego et al, 2018 ; Soung et al, 2018 ; Tsai et al, 2019 ; Wang et al, 2021a ) pathways were among the most studied ones. Accordingly, different antioxidants were tested as potential agents for the treatment of TD.…”

“…Many studies showed decreased levels of catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), either in their quantity or antioxidant capacity, upon treatment with haloperidol ( Grover et al, 2013 ; Thakur et al, 2015 ; Datta et al, 2016 ; Samad and Haleem 2017 ; Dhingra et al, 2018 ; Sonego et al, 2018 ; Tsai et al, 2019 ; Wang et al, 2021a ), reserpine ( Patil et al, 2012 ; Nade et al, 2013 ; Wang et al, 2015 ; Soung et al, 2018 ) or fluphenazine ( Schaffer et al, 2016 ). Studies have also shown that a plethora of cytokines are elevated upon treatment with antipsychotics, such as TNF- α ( Bishnoi and Boparai 2012 ; Grover et al, 2013 ; Thakur et al, 2015 ; Datta et al, 2016 ; Peroza et al, 2016 ; Sonego et al, 2018 ; Soung et al, 2018 ; Wang et al, 2021a ), IL-1 β ( Grover et al, 2013 ; Thakur et al, 2015 ; Datta et al, 2016 ; Peroza et al, 2016 ; Sonego et al, 2018 ; Wang et al, 2021a ), IL6 ( Datta et al, 2016 ; Peroza et al, 2016 ; Sonego et al, 2018 ; Soung et al, 2018 ; Wang et al, 2021a ), and IFN- γ ( Peroza et al, 2016 ). On the contrary, IL-10 is decreased, due to its role as an anti-inflammatory cytokine ( Peroza et al, 2016 ; Sonego et al, 2018 ).…”

“…On the contrary, IL-10 is decreased, due to its role as an anti-inflammatory cytokine ( Peroza et al, 2016 ; Sonego et al, 2018 ). Consequently, some agents with antioxidative and anti-inflammatory properties were tested as potential drugs for TD, such as resveratrol ( Busanello et al, 2012 , Busanello et al, 2017 ), vitamin E ( An et al, 2016 ; Shi et al, 2016 ), lycopene ( Datta et al, 2016 ), L-theanine ( Chen et al, 2018 ; Soung et al, 2018 ; Tsai et al, 2019 ), cannabidiol ( Sonego et al, 2018 ; Kajero et al, 2020 ), and catechin ( Wang et al, 2015 ; Reinheimer et al, 2020 ). Additionally, several different plant-based compounds were tested ( Patil et al, 2012 ; Sekiguchi et al, 2012 ; An et al, 2013 ; An et al, 2016 ; Shi et al, 2016 ; Samad and Haleem 2017 ; Dhingra et al, 2018 ; Wang et al, 2021a ).…”