• Hemant Tanwani
  • Pradeep Phadnis
  • Shubham Atal
  • Ritesh Churihar Department of Pharmacology, M.G.M. Medical College, A.B. Road, Indore (M.P.) India


Haloperidol, olanzapine, dopamine, serotonin subreceptor, extra pyramidal symptoms, Parkinsonism


Objective: Study to evaluate the role of serotonin in Parkinsonism by using olanzapine (an atypical antipsychotic drug) on haloperidol-induced extrapyramidal symptoms (EPS) in Swiss albino mice.

Methods: EPS like catatonia and rigidity were produced in Swiss albino mice by intraperitoneal (i. p) injection of haloperidol. Olanzapine was given as a pretreatment for acute and sub-acute basis (15 d orally) and effects were compared in terms of protection against catatonia like abnormal movements. They were analyzed statistically by ANOVA followed by post hoc Tukey's test using SPSS 20 software.

Results: There was no improvement in catatonia scores on the acute study, but on subacute (15 d) intervention a moderate improvement in the combination group (15-20 %) was seen as compared to haloperidol alone.

Conclusion: Low-dose olanzapine due to serotonin antagonism and probable partial D1 agonist actions may have the potential to improve the features of Parkinsonism. Further, it can have advantages over selective serotonin reuptake inhibitors (SSRI) for antidepressant activity in above disease.

Keywords: Haloperidol, Dopamine receptor subtypes (D1 and D2), Serotonin receptor subtypes (5HT1-7), EPS, Parkinsonism Disease (PD)


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Nyati P. Pharmacology SEED. 2nd Edition. Globalmedik [India]; 2011.

Baldesssarani RJ, Tarzai FI. Drug therapy of psychosis and mania in the pharmacological basis of therapeutics. 12thEdition. McGraw Hill [New York]; 2011. p. 461-80.

Sharma HL, Sharma KK. Principles of pharmacology. 2ndEdition. Paras Publications, Hyderabad [India]; 2012.

Vogel HG. Evaluation of extrapyramidal symptoms in rats. Drug Discovery and evaluation pharmacological assays. 2nd Edition. Springer Verlag, Berlin [Heidelberg]; 2002.

Nayyar T, Bubser M, Ferguson MC, Neely MD, Goodwin JS, Montine TJ, et al. Cortical serotonin and norepinephrine denervation in parkinsonism. Eur J Neurosci 2009;30:207-16.

Silva SR, Fuloro Neto HA, Pires JG. Effects of 5HT3 receptor antagonists on neuroleptic induced catalepsy in mice. Neuropharmacology 1995;34:97-9.

Fox SH, Chuang R, Brotchie JM. Serotonin and Parkinson’s disease: on movement, mood and madness. Mov Disord 2009;24:1255-66.

Daw ND, Kakade S, Dayan P. Opponent interactions between serotonin and dopamine. Neural Networks 2002;15:603-16.

Van Erp AM, Miczek KA. Aggressive behavior, increased accumbal dopamine and decreased cortical serotonin in rats. J Neurosci 2000;20:9320-5.

Seo D, Patrick CJ, Kennealy PJ. Role of serotonin and dopamine system interventions in the neurobiology of impulse aggression and its co morbidity with other clinical disorders. Aggresion Violent Behavior 2008;5:383-95.

DeBattista C. Antipsychotic agents and lithium. In: Katzung BG, Trevor AJ. Eds. Basic and clinical pharmacology. 13th Edition. McGraw Hill [New Delhi]; 2015. p. 490-509.

Invernizzi RW, Pierucci M, Calcagno E. Selective activation of 5HT(2C) receptors stimulates GABA-ergic function in the rat substantia nigra pars reticularis: a combined in vivo electro brain amines in the rhesus monkey. Neuroscience 1991; 44:591-605.

Gulley LR, Nemeroff CB. Biological basis of anxiety depression. J Clin Psychiatry 1993;54(Suppl I):16-9.

Madhusooan S, Alexeenko L, Sanders R, Brenner R. Extra pyramidal symptoms associated with antidepressants-A review of the literature and analysis of spontaneous reports. Ann Clin Psychiatry 2010;22:148-56.

Ng KY, Chase TN, Colburn RW, Kopin IJ. Dopamine stimulation induced release from central neurons. Science 1971;172:487-9.

Tanaka H, Kannar IK, Tomiyama M, Suda T. Role of serotonin neurons in levodopa derived extracellular dopamine in the striatum of 6-OHDA-lesioned rats. Neuroreport 1999;10:631-4.

Carta M, Carlsson T, Kirik T, Bjourklund A. The dopamine released from 5HT terminals is the cause of levodopa induced dyskinesia in Parkinsonian rats. Brain 2007;130:1819-33.

Santiago M, Matarredona ER, Machado A, Cano J. Influence of serotoninergic drugs on in vivo dopamine extracellular output in rat striatum. J Neurosci Res 1998;52:591-810.

Doder M, Rabiner EA, Turjanski N, Lees AJ, Brooks DJ<>. Tremors in parkin’s disease and serotonergic dysfunction; an 11C-WAY 100635 PET study. Neurology 2003;60:601-5.

Kerenyi L, Ricaurete GA, Schrelten DJ, Mccann U, Varga J, Mathews W, et al. Positron emission tomography of striatal serotonin transporters in Parkinson’s disease. Arch Neurol 2003;60:1223-9.

Numan S, Lundgren KH, Wright DE, Herman JP. Increased expression of 5HT2 receptor m RNA in rat striatum following 6-OHDA lesions of the adult nigrostriatal pathways. Brain Res Mol Brain Res 1995;29:391-6.

Ninan I, Kulkarni SK. Differential effects of olanzapine at dopamine D1 and D2 receptors in dopamine depleted animals. Psychopharmacology 1999;142:175-81.

Durif F, Debilly B, Galitzky M, Morand D, Viallet F, Borg M, et al. Clozapine improves dyskinesias in Parkinson disease a double-blind, placebo-controlled study. Neurology 2004;62:381-8.

Vanover KE, Betz AJ, Weber SM, Bibbiani F, Kielaite A, Weiner DM, et al. A 5HT (2A) receptor inverse agonist (ACP-103) reduces tremors in a rat model and levodopa induced dyskinesias in a monkey model. Pharmacol Biochem Behav 2008;62:540-4.



How to Cite

Tanwani, H., P. Phadnis, S. Atal, and R. Churihar. “STUDY TO EVALUATE THE ROLE OF SEROTONIN IN PARKINSONIAN SYMPTOMS”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 7, July 2016, pp. 209-11,



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