TheParkinson’s disease (PD) is one of the common neurodegenerative disorders whichcan also be induced by administration of antipsychotic drugs while treatingpositive symptoms of schizophrenia. But motor disorders likedyskinesia,rigidity and tremors can also result from chronic neuroleptictreatment. The neuroleptic induced neurological disorders may not be improvedby the supplement of dopamine due to chronic blockade of dopamine D2 receptorsby the neuroleptic drugs like phenothiazine compounds. The hypothesis ofdopamine receptor supersensitivity proposes that antipsychotic drug treatment causes hypersensitization ofdopamine D2 receptors. There is no single laboratory model to evaluate parkinsonism and inwhich a proper evaluation of antiparkinsonian activity can be carried out.However, there is a positive correlation between catatonia in the laboratoryanimals and the extrapyramidal symptoms produced by neuroleptics in humans.
So,Morpurgodescribed a direct method to screen the drugs affecting dopamine receptors. Heinduced catatonia which is a state of neurogenic motor immobility andbehavioural abnormality manifestations with stupor.3 The occurrence and irreversibility ofthis neurological disorder with motor immobility in drug induced parkinsonismhas been considered as a major clinical issue in the treatment of schizophrenicpatients.4The searchfor new drugs is needed to avoid suchside effects caused while treating schizophrenia.
The aqueous extract of Curcumin longa being a herbalproduct has a tendency of passingthrough blood brain barrier (BBB) and also has antioxidant activity, which mayprove effective in treating drug induced PD and related neuropsychiatry disorders. 4.Objectives: The objective of thisstudy will be- i) to induce catatonia in mice withhaloperidol. ii) to evaluate theeffects of the aqueous extract of Curcuminlonga on dopaminergic neurotransmission in haloperidol induced motordysfunction. 5.Methodology:Type of the study: Experimentalanimal studySample size : 30 mice, 5 groups with 6 mice in each group.
Site of study : Depart ofpharmacology, Pondicherry institute of medicalsciences.(PIMS)Study period : June to July, 2018(2 months) Procedure: The IAEC approval will be obtained to conduct thestudy. It is an animal study using Swiss albino male mice. The mice fromCentral Animal House, PIMS will be used for this study.The aqueous extract of Curcumin longa will be procured from acompetent herbal drug manufacturer with complete phytochemical constituentsfurnished by the manufacturer.
Swiss albino male mice weighing 25 to 30 gm andof 60 to 90 days old will be used in this study. This will be maintained inplastic cages under contolled lighting conditions (12h light/12h dark regime),relative humidity(50±5%) and temperature (37±2ºC). They will be fed withpellets and provided ad libitum access to water. Actophotometerand other instruments necessary in Morpurgo method can be used in the Dept ofPharmacology for this study. Haloperidol will beadministered in the dosage of 1mg/kg of body weight/day/animal4 intraperitoneally for 15 days.The assessment will be done as per Morpurgo scoring method weekly after 24hours of the last dosage (on 8th and 15th day).
The 1st group of 6 mice will be treatedwith vehicle and rest of the groups will be treated with haloperidol. The 3rd, 4th and 5th groups of mice will bepretreated with the aqueous extract of Curcuminlonga 50mg, 100mg and 200mg/kg ofbody weight respectively as per the protocol listed below: GROUP 1: Controlgroup with 6 mice will be treated only with vehicle (sterile water) for 15 days. GROUP 2: Control group with 6mice will be treatedwith haloperidol for 15 days. GROUP 3: Experimental group with 6 mice willbe pretreated with the aqueous extract of Curcuminlonga 50mg/kg of body weight /day/animal intraperitoneally for 15days. Haloperidol will be administered 50 mins after Curcumin longa administration for 15days. GROUP 4: Experimental group with 6 mice will be pretreated with aqueous extract ofCurcumin longa 100 mg/kg of bodyweight/day/animal intraperitoneally for 15 days. Haloperidol will be administered 50mins after Curcumin longa administration for 15 days. GROUP 5: Experimental group with 6 mice will be pretreatedwith aqueous extract of Curcumin longa 200mg/kgof body weight/day/animal intraperitoneally for 15 days.
Haloperidol will beadministered 50 mins after Curcumin longaadministration for 15 days. The locomotor activity andMorpurgo catatonia scoring of control and experimental animals will be measuredby using actophotometer and Morpurgo methods respectively on 8th and 15th day before drug administration.The data observed as per the table given above and this will be tabulated forstatistical analysis. Methodsof statistical analysis & test applied: All the results will be expressed as mean ± SEM.Data will be analyzed by one way analysis of variance (ANOVA) followed by Turkey’smultiple comparison test using SPSS 11 software. p<0.
05 will be consideredas statistically significant. 6.Implications: The Curcumin longa can be used as adjuvanttherapy in the treatment of neuropsychiatry disorders such as schizophrenia.This method is emphasised in this study to evaluate antiparkinsonian activityin drug induced parkinsonism by using aqueous extract of Curcumin longa in haloperidol induced catatonia. This can openavenue for adjuvant therapy which can be used with neuroleptic drugs that willavoid untoward effects while treatingthe schizophrenic patients.
Thus the aqueous extract of Curcumin longa can reducethe socioeconomic burdens and side effects caused by existing neurolepticdrugs. 7.References: 1. Forno LS. Neuropathology of Parkinson’s disease.
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2. Dhingra, Dinesh,Gahalain, Nidhi. Amelioration ofHaloperidol-Induced Orofacial Dyskinesia And Catalepsy By Ellagic Acid In Rats.International Journal of Research in Ayurveda & Pharmacy.
Mar-Apr 2016;7(Suppl 2): 222-227. 3. Jesudoss Prabhakar et al. Methods used in screening antiparkinsonactivity: Errors in published literature.
International Journal ofPharmacological Research. 2017; 7(05): 98. 4.
Bishnoi et al. (2008). Protective effect of Curcumin, theactive principle of turmeric (Curcuma longa) in haloperidol- induced orofacialdyskinesia and associated behavioural, biochemical and neurochemical changes inrat brain.
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5. Essa MM, Vijayan RK, Castellano-Gonzalez G, Memon MA, Braidy N,Guillemin GJ.Neuroprotective effect of natural products against Alzheimer’sdisease.
Neurochem Res2012;37:1829-42. STAGE BEHAVIOUR SCORE STAGE-0 Mouse moves normally, when placed on the table. 0 STAGE-1 Mouse moves only, when touched or pushed. 0.
5 STAGE-2 No movements can be seen in mouse ,even upon eliciting. 0.5 STAGE-3 Mouse placed on the table with one of the front paws raised on a 3cm block, fails to correct the posture in 10 seconds. 0.5 for one paw, therefore 0.5×2=1.
STAGE-4 Mouse placed on the table with one of the front paws raised on a 9cm block fails to correct the posture. 1 for one paw = 1×2=2 Table 1: The severity of catatoniainduced by haloperidol in mice is scored as follows