TITLE:
Vitamin D3 Receptor Activation Rescued Corticostriatal Neural Activity and Improved Motor Function in –D2R Tardive Dyskinesia Mice Model
AUTHORS:
Oluwamolakun O. Bankole, Babafemi J. Laoye, Mujittapha U. Sirjao, Azeez O. Ishola, Damilola E. Oyeleke, Wasiu G. Balogun, Amin Abdulbasit, Ansa E. Cobham, Ibukun D. Akinrinade, Olalekan M. Ogundele
KEYWORDS:
Haloperidol, VD3R, Dyskinesia, D2R, Neural Activity, Corticostriatal
JOURNAL NAME:
Journal of Biomedical Science and Engineering,
Vol.8 No.8,
August
20,
2015
ABSTRACT: Haloperidol-induced dyskinesia has been linked to a reduction in dopamine activity characterized by the inhibition of dopamine receptive sites on D2-receptor (D2R). As a result of D2R inhibition, calcium-linked neural activity is affected and seen as a decline in mo-tor-cognitive function after prolonged haloperidol use in the treatment of psychotic disorders. In this study, we have elucidated the relationship between haloperidol-induced tardive dyskinesia and the neural activity in motor cortex (M1), basal nucleus (CPu), prefrontal cortex (PFC) and hippocampus (CA1). Also, we explored the role of Vitamin D3 receptor (VD3R) activation as a therapeutic target in improving motor-cognitive functions in dyskinetic mice. Dyskinesia was induced in adult BALB/c mice after 28 days of haloperidol treatment (10 mg/Kg; intraperitoneal). We established the presence of abnormal involuntary movements (AIMs) in the haloperidol treated mice (-D2) through assessment of the threshold and amplitude of abnormal involuntary movements (AIMs) for the Limbs (Li) and Orolingual (Ol) area (Li and Ol AIMs). As a confirmatory test, the dyskinetic mice (-D2) showed high global AIMs score when compared with the VD3RA intervention group (-D2/+VDR) for Li and Ol AIMs. Furthermore, in the behavioral tests, the dyskinetic mice exhibited a decrease in latency of fall (LOF; Rotarod-P 2/+VDR), 100 mg/Kg for 7 days, CPu-CA1 burst activity was restored leading to a decrease in abnormal movement, and an increase in motor function. Ultimately, we deduced that VD3RA activation reduced the threshold of abnormal movement in haloperidol induced dyskinesia.