Abstract
Long-term treatment with haloperidol is associated with a number of extrapyramidal side effects. This limitation presents a marked therapeutic challenge. The present method (21 days administration of haloperidol, 5 mg/kg, i.p.) has been established to gain deeper insight into the molecular etiology (inflammation and apoptosis) of haloperidol-induced cellular death. In the present model, besides the corresponding increase in the vacuous chewing movements (VCMs), enhanced oxidative stress, there was a significant increase in cellular markers of inflammation and apoptotic protein (caspase-3), leading to cellular death. We also suggest that this model will be effective in preclinical testing of new chemical entities for the treatment of haloperidol induced tardive dyskinesia and related symptoms.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Creese, I., Burt, D., Snyder, S.H. (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science. 192,481–483.
Walker, J.M., Bowen, W.D., Walker, F.O., Matsumoto, R.R., De Costa, B., Rice, C.K. (1990) Sigma receptors: biology and function. Pharmacol. Rev. 42,355–402.
Vilner, B.J., Costa, B.R., Bowen, W.D. (1995) Cytotoxic effects of sigma ligands: Sigma receptor-mediated alterations in cellular morphology and viability. J Neurosci. 15,117–134.
Meshul, C.K. and Tan, S.E, (1994) Haloperidol-induced morphological alterations are associated with changes in calcium/calmodulin kinase II activity and the glutamate immunoreactivity. Synapse. 18, 205–217.
Halliday, G.M., Pond, S.M., Cartwright, H., McRitchie, D.A., Castagnoli, N., Van der Shyf, C.J. (1999) Clinical and neuropathological abnormalities in baboons treated with HPTP, tetrahydropyridine analog of haloperidol. Exp. Neurol. 158,155–163.
Post, A., Rücker, M., Ohl, F., Uhr, M., Holsboer, F., Almeida, O.F., Michaelidis, T.M. (2002) Mechanisms underlying the protective potential of alpha-tocopherol (vitamin E) against haloperidol-associated neurotoxicity. Neuropsychopharmacology. 26, 397–407.
Sagara, Y. (1998) Induction of reactive oxygen species in neurons by haloperidol. J. Neurochem. 71,1002–1012.
Lohr, J.B., Cadet, J.L., Lohr, M.A., Larson, L., Wasli, E., Wade, L., Hylton, R., Vidoni, C., Jeste, D.V., Wyatt, R.J. (1988) Vitamin E in the treatment of tardive dyskinesia: The possible involvement of free radical mechanism, Schizophr. Bull. 14,291–296.
Wills, E.D. (1966) Mechanism of lipid peroxide formation in animal tissues. Biochem. Jour. 99, 667–676.
Babior, B.M., Kipner, R.S., Cerutte, J.T. (1973) Biological defense mechanism. The production by leukocytes of superoxide, a potential bacterial agent. J. Clin. Investigation. 52,741–744.
Ellman, G.L. (1959) Tissue sulfhydryl groups. Arch. of Biochemi. Biophy. 82, 70–77.
Lowry, O.H. (1951) Protein measurements with the Folin-phenol reagent. J. Biol. Chem. 193, 265–275
Bishnoi, M., Chopra, K., Kulkarni, S.K. (2007) Possible anti-oxidant and neuroprotective mechanisms of zolpidem in attenuating typical anti-psychotic-induced orofacial dyskinesia-A biochemical and neurochemical study.Prog. Neuropsychopharmacol. Biol. Psychiatry. 31,1130–1138.
Acknowledgment
The authors would like to thank Professor S.K. Kulkarni and Dr. Kanwaljit Chopra for their guidance and support.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Bishnoi, M., Boparai, R.K. (2012). An Animal Model to Study the Molecular Basis of Tardive Dyskinesia. In: Kobeissy, F. (eds) Psychiatric Disorders. Methods in Molecular Biology, vol 829. Humana Press. https://doi.org/10.1007/978-1-61779-458-2_12
Download citation
DOI: https://doi.org/10.1007/978-1-61779-458-2_12
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-457-5
Online ISBN: 978-1-61779-458-2
eBook Packages: Springer Protocols