Objective: To investigate the neuroprotective effect of raloxifene and fulvestrant on behavioral, biochemical, neurochemical, and molecular alterations in a haloperidol-induced animal model of Tardive dyskinesia.

To investigate the effect of raloxifene and fulvestrant on immunohistopathological alteration in striatal tissues on haloperidol-injected Rats.

To explore the molecular mechanism of raloxifene and fulvestrant by using GPR30 agonist and antagonist in rats.

Background: Tardive dyskinesia is a severe movement disorder that occurs during the long-term administration of antipsychotic medication, mainly prescribed to treat schizophrenia. Antipsychotic was discovered as a dopaminergic receptor blocking agent that specifically targets the dopaminergic D2 receptor and controls movements

Method: Adult 8-week-old Male Wistar rats weighing 180 to 250 g were utilized for the in-vivo study; all behavior parameters were performed on 13 groups. Biochemical, neurochemical, and western blotting were performed on n=6 animals. ELISA kits were utilized for inflammatory and apoptotic markers, and CST antibodies were preferred for western blot.

Results: Raloxifene and fulvestrant 5 and 10 mg/kg treatment significantly improved the behavior activity including motor coordination, grip strength, and locomotor activity in rats treated with haloperidol. Moreover, haloperidol exposure substantially increased oxidative stress as compared to the control group. While treatment of raloxifene and fulvestrant significantly restored antioxidant enzyme activity and reduced inflammatory (TNF-α and IL-1β) and apoptotic (Caspase 3, 6, & 9) markers in the striatum of rats treated with haloperidol. Moreover, raloxifene and fulvestrant treatment improved the expression of GPR30, PI3k, Akt and Nrf2 signaling pathways in haloperidol-treated rats.

Conclusion: Study findings suggested that raloxifene and fulvestrant have strong antioxidant, anti inflammatory, and anti apoptotic properties, which help to ameliorate the antipsychotic induced tardive dyskinesia like movement. findings also suggested that raloxifene and fulvestrant have neuroprotective abilities. It could be used as a treatment option for neurological disorders, including tardive dyskinesia.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/exploring-the-neuroprotective-potential-of-raloxifene-and-fulvestrant-against-haloperidol-induced-parkinson-disease-insights-into-gpr30-pi3k-akt-nrf2-signaling-pathways/