Vitamin D₃ Receptor Activation Rescued Corticostriatal Neural Activity and Improved Motor Function in –D₂R Tardive Dyskinesia Mice Model

Oluwamolakun O. Bankole¹, Babafemi J. Laoye¹, Mujittapha U. Sirjao², Azeez O. Ishola², Damilola E. Oyeleke², Wasiu G. Balogun³, Amin Abdulbasit⁴, Ansa E. Cobham⁵, Ibukun D. Akinrinade^6,7, Olalekan M. Ogundele^2*

¹Department of Biological Sciences, College of Sciences, Afe Babalola University, Ado-Ekiti, Nigeria.
²Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria.
³Department of Anatomy, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.
⁴Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.
⁵Department of Anatomy, College of Medicine, University of Calabar, Calabar, Nigeria.
⁶Instituto Gulbenkian de Ciencia, Oerias, Portugal.
⁷Department of Anatomy, Bingham University College of Medicine, Karu, Nigeria.

DOI: 10.4236/jbise.2015.88049                

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 < 0.05), climbing attempts (Cylinder test; P < 0.05) and latency of Turning (Parallel bar test; LOT-P < 0.05) when compared with the control. The reduced motor function in dyskinetic mice was associated with a decline in CPu-CA1 burst frequencies and an increase in M1-PFC cortical activity. However, after VD3RA intervention (-D₂/+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.

Keywords

Haloperidol, VD₃R, Dyskinesia, D₂R, Neural Activity, Corticostriatal

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Gardos, G. (1999) Managing Antipsychotic-Induced Tardive Dyskinesia. Drug Safety, 20, 187-193. http://dx.doi.org/10.2165/00002018-199920020-00007
[2]	Zhang, S., Xie, C., Wang, Q. and Liu, Z. (2014) Interactions of CaMKII with Dopamine D2 Receptors: Roles in Levodopa-Induced Dyskinesia in 6-Hydroxydopamine Lesioned Parkinson’s Rats. Scientific Reports, 29, 6811. http://dx.doi.org/10.1038/srep06811
[3]	Calabresi, P., Picconi, B., Tozzi, A., Ghiglieri, V. and Di Filippo, M. (2014) Direct and Indirect Pathways of Basal Ganglia: A Critical Reappraisal. Nature Neuroscience, 17, 1022-1030. http://dx.doi.org/10.1038/nn.3743
[4]	Chun, L.S., Free, R.B., Doyle, T.B., Huang, X.P., Rankin, M.L. and Sibley, D.R. (2013) D1-D2 Dopamine Receptor Synergy Promotes Calcium Signaling via Multiple Mechanisms. Molecular Pharmacology, 84, 190-200. http://dx.doi.org/10.1124/mol.113.085175
[5]	Ma, L.Q., Liu, C., Wang, F., Xie, N., Gu, J., Fu, H., Wang, J.H., Cai, F., Liu, J. and Chen, J.G. (2009) Activation of Phosphatidylinositol-Linked Novel D1 Dopamine Receptors Inhibits High-Voltage-Activated Ca2+ Currents in Primary Cultured Striatal Neurons. Journal of Neurophysiology, 101, 2230-2238. http://dx.doi.org/10.1152/jn.90345.2008
[6]	Yang, M.C., Chen, K.P. and Lung, F.W. (2014) Generalized Estimating Equation Model and Long-Term Exposure Effect of Antipsychotics on SH-SY5Y Cells against Oxidative Stressors. European Journal of Pharmacology, 5, 697-702. http://dx.doi.org/10.1016/j.ejphar.2014.06.007
[7]	Nagano-Saito, A., Martinu, K. and Monchi, O. (2014) Function of Basal Ganglia in Bridging Cognitive and Motor Modules to Perform an Action. Frontiers in Neuroscience, 8, 187.
[8]	Lawson, R.A., Yarnall, A.J., Duncan, G.W., Khoo, T.K., Breen, D.P., Barker, R.A., Collerton, D., Taylor, J.P. and Burn, D.J. (2014) Severity of Mild Cognitive Impairment in Early Parkinson’s Disease Contributes to Poorer Quality of Life. Parkinsonism & Related Disorders, 20, 1071-1075. http://dx.doi.org/10.1016/j.parkreldis.2014.07.004
[9]	Scatton, B., Worms, P., Lloyd, K.G. and Bartholini, G. (2008) Cortical Modulation of Striatal Function. Pharmacology, Biochemistry and Behavior, 90, 226-235. http://dx.doi.org/10.1016/j.pbb.2008.04.011
[10]	Mao, L.M., Xue, B., Jin, D.Z. and Wang, J.Q. (2015) Dynamic Increases in AMPA Receptor Phosphorylation in the Rat Hippocampus in Response to Amphetamine. Journal of Neurochemistry, Published Online. http://dx.doi.org/10.1111/jnc.13067
[11]	Taepavarapruk, P., Butts, K.A. and Phillips, A.G. (2014) Dopamine and Glutamate Interaction Mediates Reinstatement of Drug-Seeking Behavior by Stim-ulation of the Ventral Subiculum. International Journal of Neuropsychopharmacology, 18, No. 1, pii: pyu008.
[12]	Avshalumov, M.V., Chen, B.T., Marshall, S.P., Pena, D.M. and Rice, M.E. (2003) Glutamate-Dependent Inhibition of Dopamine Release in Striatum Is Mediated by a New Diffusible Messenger, H2O2. The Journal of Neuroscience, 23, 2744-2750.
[13]	Ogundele, O.M., Nanakumo, E.T., Ishola, A.O., Obende, O.M., Enye, L.A., Balogun, W.G., Cobham, A.E. and Abdulbasit, A. (2014) -NMDA R/+VDR Pharmacological Phenotype as a Novel Therapeutic Target in Relieving Motor-Cognitive Impairments in Parkinsonism. Drug and Chemical Toxicology, 4, 1-13. http://dx.doi.org/10.3109/01480545.2014.975355
[14]	Bhattachary, S.K., Bhattacharya, D. and Muruganandam, A.V. (2000) Effect of Emblica Officinalis Tannoids on a Rat Model of Tardive Dyskinesia. Indian Journal of Experimental Biology, 38, 945-947.
[15]	Cenci, M.A., Ohlin, K.E. and Odin, P. (2011) Current Options and Future Possibilities for the Treatment of Dyskinesia and Motor Fluctuations in Parkinson’s Disease. CNS & Neurological Disorders—Drug Targets, 10, 670-684. http://dx.doi.org/10.2174/187152711797247885
[16]	Deacon, R.M. (2013) Measuring Motor Coordination in Mice. Journal of Visualized Experiments, No. 75, e2609. http://dx.doi.org/10.3791/2609
[17]	Kozelj, S. and Baker, S.N. (2014) Different Phase Delays of Peripheral Input to Primate Motor Cortex and Spinal Cord Promote Cancellation at Physiological Tremor Frequencies. Journal of Neurophysiology, 111, 2001-2016. http://dx.doi.org/10.1152/jn.00935.2012
[18]	Krabbe, S., Duda, J., Schiemann, J., Poetschke, C., Schneider, G., Kande, E., Liss, B., Roeper, J. and Simpson, E. (2015) Increased Dopamine D2 Receptor Activity in the Striatum Alters Firing Pattern of Dopamine Neurons in the Ventral Tegmental Area. Proceedings of the National Academy of Sciences of the United States of America, 112, E1498-E1506. http://dx.doi.org/10.1073/pnas.1500450112
[19]	Zhang, X.Y., Zhou, D.F., Cao, L.Y., Xu, C.Q., Chen, D.C. and Wu, G.Y. (2004) The Effect of Vitamin E Treatment on Tardive Dyskinesia and Blood Superoxide Dismutase: A Double-Blind Placebo-Controlled Trial. Journal of Clinical Psychopharmacology, 24, 83-86. http://dx.doi.org/10.1097/01.jcp.0000104912.75206.2b
[20]	Egan, M.F., Hyde, T.M., Albers, G.W., Elkashef, A., Alexander, R.C., Reeve, A., Blum, A., Saenz, R.E. and Wyatt, R.J. (1992) Treatment of Tardive Dyskinesia with Vitamin E. American Journal of Psychiatry, 149, 773-777. http://dx.doi.org/10.1176/ajp.149.6.773
[21]	Woods, J.L. (2011) Limb Shaking, Vomiting and Vitamin D Deficiency. The Journal of the Arkansas Medical Society, 107, 284-286.
[22]	Golan, D., Staun-Ram, E., Glass-Marmor, L., Lavi, I. Rozenberg, O., Dishon, S., Barak, M., Ish-Shalom, S. and Miller, A. (2013) The Influence of Vitamin D Supplementation on Melatonin Status in Patients with Multiple Sclerosis. Brain, Behavior, and Immunity, 32, 180-185. http://dx.doi.org/10.1016/j.bbi.2013.04.010
[23]	Groves, N.J., McGrath, J.J. and Burne, T.H. (2014) Vitamin D as a Neurosteroid Affecting the Developing and Adult Brain. Annual Review of Nutrition, 34, 117-141. http://dx.doi.org/10.1146/annurevnutr-071813-105557
[24]	Lindenbach, D. and Bishop, C. (2013) Critical Involvement of the Motor Cortex in the Pathophysiology and Treatment of Parkinson’s Disease. Neuroscience & Biobehavioral Reviews, 37, 2737-2750. http://dx.doi.org/10.1016/j.neubiorev.2013.09.008
[25]	Shen, W., Flajolet, M., Greengard, P. and Surmeier, D.J. (2008) Dichotomous Dopaminergic Control of Striatal Synaptic Plasticity. Science, 321, 848-851. http://dx.doi.org/10.1126/science.1160575
[26]	Wang, Y. and Goldman-Rakic, P.S. (2004) D2 Receptor Regulation of Synaptic Burst Firing in Prefrontal Cortical Pyramidal Neurons. Proceedings of the National Academy of Sciences of the United States of America, 101, 5093-5098. http://dx.doi.org/10.1073/pnas.0400954101