The catatonia which is a state of neurogenic motor

  The
Parkinson’s disease (PD) is one of the common neurodegenerative disorders which
can also be induced by administration of antipsychotic drugs while treating
positive symptoms of schizophrenia. But motor disorders like
dyskinesia,rigidity and tremors can also result from chronic neuroleptic
treatment. The neuroleptic induced neurological disorders may not be improved
by the supplement of dopamine due to chronic blockade of dopamine D2 receptors
by the neuroleptic drugs like phenothiazine compounds. The hypothesis of
dopamine receptor supersensitivity proposes that antipsychotic  drug treatment causes hypersensitization of
dopamine D2 receptors. There is no single laboratory model to evaluate parkinsonism and in
which a proper evaluation of antiparkinsonian activity can be carried out.
However, there is a positive correlation between catatonia in the laboratory
animals and the extrapyramidal symptoms produced by neuroleptics in humans. So,
Morpurgo
described a direct method to screen the drugs affecting dopamine receptors. He
induced catatonia which is a state of neurogenic motor immobility and
behavioural abnormality manifestations with stupor.3  The occurrence and irreversibility of
this neurological disorder with motor immobility in drug induced parkinsonism
has been considered as a major clinical issue in the treatment of schizophrenic
patients.4The search
for new drugs  is needed to avoid such
side effects caused while treating schizophrenia.

       The aqueous extract of Curcumin longa being a herbal
product  has a tendency of passing
through blood brain barrier (BBB) and also has antioxidant activity, which may
prove effective in treating drug induced  PD and related neuropsychiatry disorders.

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4.Objectives:

 

The objective of this
study will be-

 i) to induce catatonia in mice with
haloperidol.

ii) to evaluate the
effects of the aqueous extract of Curcumin
longa on dopaminergic  neurotransmission in haloperidol induced motor
dysfunction.

 

5.Methodology:

Type of the study: Experimental
animal study

Sample size         
: 30 mice, 5 groups with 6 mice in each group.

Site of study         : Depart of
pharmacology, Pondicherry institute of

                                 medical
sciences.(PIMS)

Study period       
: June to July, 2018(2 months)

 

Procedure:

 

The IAEC approval will be obtained to conduct the
study. It is an animal study using Swiss albino male mice. The mice from
Central Animal House, PIMS will be used for this study.The aqueous extract of Curcumin longa will be procured from a
competent herbal drug manufacturer with complete phytochemical constituents
furnished by the manufacturer. Swiss albino male mice weighing 25 to 30 gm and
of 60 to 90 days old will be used in this study. This will be maintained in
plastic cages under contolled lighting conditions (12h light/12h dark regime),
relative humidity(50±5%) and temperature (37±2ºC). They will be fed with
pellets and provided  ad libitum access to water. Actophotometer
and other instruments necessary in Morpurgo method can be used in the Dept of
Pharmacology for this study.

 

    Haloperidol will be
administered 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 24
hours of the last dosage (on 8th and 15th day). The 1st group of 6 mice will be treated
with vehicle and rest of the groups will be treated with haloperidol. The 3rd, 4th and 5th groups of mice will be
pretreated with the aqueous extract of Curcumin
longa  50mg, 100mg and 200mg/kg of
body weight respectively as per the protocol listed below:

 

   GROUP 1:

 

          Control
group with 6 mice will be treated only with vehicle (sterile water) for 15 days.

 

         GROUP 2:

 

           Control group with 6mice will be treated
with haloperidol for 15 days.

 

GROUP 3:

 

  Experimental group with 6 mice will
be pretreated with the aqueous extract of Curcumin
longa 50mg/kg of body weight /day/animal intraperitoneally for 15days. Haloperidol  will be administered 50 mins after Curcumin longa administration for 15
days.

 

GROUP 4:

 

Experimental group with 6 mice will be pretreated with aqueous extract of
Curcumin longa 100 mg/kg of body
weight/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 pretreated
with aqueous extract of Curcumin longa 200mg/kg
of body weight/day/animal intraperitoneally for 15 days. Haloperidol will be
administered 50 mins after Curcumin longa
administration for 15 days.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

       

 

 

 

        The locomotor activity and
Morpurgo catatonia scoring of control and experimental animals will be measured
by 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 for
statistical analysis.

 

Methods
of 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’s
multiple comparison test using SPSS 11 software. p<0.05 will be considered as statistically significant.         6.Implications:   The Curcumin longa can be used as adjuvant therapy in the treatment of neuropsychiatry disorders such as schizophrenia. This method is emphasised in this study to evaluate antiparkinsonian activity in drug induced parkinsonism by using aqueous extract of Curcumin longa in haloperidol induced catatonia. This can open avenue for adjuvant therapy which can be used with neuroleptic drugs that will avoid  untoward effects while treating the schizophrenic patients. Thus the aqueous extract of Curcumin longa  can reduce the socioeconomic burdens and side effects caused by existing neuroleptic drugs.     7.References:   1. Forno LS. Neuropathology of Parkinson's disease. J. Neuropathol. Exp.   Neurol.1996;55:259–72.   2.  Dhingra, Dinesh,Gahalain, Nidhi. Amelioration of Haloperidol-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 antiparkinson activity:   Errors in published literature. International Journal of Pharmacological Research. 2017; 7(05): 98.   4.  Bishnoi et al. (2008). Protective effect of Curcumin, the active principle of turmeric (Curcuma longa) in haloperidol- induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes in rat brain. Pharmacology, biochemistry, and behavior. 88. 511-22. 0.1016/j.pbb.2007.10.009.   5.  Essa MM, Vijayan RK, Castellano-Gonzalez G, Memon MA, Braidy N, Guillemin GJ. Neuroprotective effect of natural products against Alzheimer's disease. Neurochem Res 2012;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 catatonia induced by haloperidol in mice is scored as follows