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Journal - 5.cdr

DOPAMINE-D AND SEROTONIN- 5HT RECEPTOR MEDIA AMINE-D AND SEROTONIN- 5HT RECEPTOR MEDIA ABSTRACT
secondary dysfunction of central neurotransmitter Recent evidence suggests that overactivity of systems including among others, dopamine and central serotonin 5- HT and dopamine D receptors is involved in the pathogenesis of schizophrenia and that central serotonin 5 HT2 receptor antagonism antipsychotics is correlated with their in vitro has been associated with efficacy against negative symptoms of schizophrenia and a lower propensity antagonistic activity has been associated with to cause extrapyramidal side effects. Risperidone, an atypical antipsychotic agent has both dopamine schizophrenia and a lower propensity to cause D and serotonin 5- HT antagonistic activity. To Therefore taking into account above reports, the present study was conceived so as to study the effect of risperidone on central dopamine D and stereotyped behavior in rats. Risperidone was also serotonin 5-HT receptor mediated behaviours in studied for its effect on 5- hydroxytryptophan induced head twitch activity in mice, a central OBJECTIVES
demonstrating central 5-HT receptor antagonism.
It was observed that risperidone antagonized the Apomorphine induced stereotyped behavior in stereotyped behavior in rats as well as the 5- activity in mice, in a dose dependent manner which shows that risperidone combines both central MATERIALS AND METHODS
Key words
Preparation of solutions:
Drug used Solvent
Negative symptoms Extrapyramidal side effects Apomorphine HCl Distilled water containing 0.2 INTRODUCTION
Risperidone, a benzisoxazole derivative is an atypical (Methedrine inj, Borroughs Welcome & Co, 30 schizophrenia are now well established, the etiology and pathophysiology of the disease remain unclear.
There is emerging evidence for specific neuronal International Journal of Basic Medical Science - August 2012, Vol : 3, Issue : 3 Chandrakant Sahebrao Waghmare et al, Effect of Risperidone, An The strengths of the solution were so adjusted that were made between 10 and 16 hours at 240 -260 c in the required dose of the drug was present in a a noiseless, diffusely illuminated room. For observation volume of 0.1 ml/10gm body weight in mice and 0.2 animals were placed in open topped transparent plastic cages measuring 30 X 20 X 20 cms.
All the drugs were injected intraperitoneally.
The mice were divided in groups of 6 each. The control group received carbidopa 25 mg/kg i.p.
stereotyped behavior, male albino rats weighing followed 15 minutes later by 5- hydroxytryptophan 100 mg/kg i.p. The test group in addition received standard diet and tap water were used. Each animal risperidone 60 minutes before. The assessment of head twitch activity was done by method of Guy M.
Gudwin, Richard Green et al, (1985) .
All observations were made between 10 and 16 illuminated room. For observations, the animals hydroxytryptophan injection, total no. of head were placed in individual cages made of wire netting twitches in a 2 minute period were noted. The with a floor of 30 cm X 20 cm X 20 cm. The animals results were statistically analyzed by Mann Whitney were placed in observation cages 30 minutes before OBSERVATIONS & RESULTS
The intensity of stereotyped behavior was assessed apomorphine induced stereotyped behavior in over an observation period at 10 min. intervals rats in a dose dependent manner. (Table 1) throughout its duration using the scoring system of behavior in rats in a dose dependent manner.
head twitch activity in mice induced by 5 HTP in Intensity
S.B. score
Treatment dose (mg/kg)
‘P’ value
The maximum intensity of stereotyped behavior scored by each rat in the group was taken to compute the mean value of the group.
Drugs were injected intraperitoneally (i.p). For each dose 10 animals were used. Risperidone was before receiving apomorphine / methamphetamine.
The results were statistically analyzed by the For studying effect of risperidone on head twitch activity in mice, male albino mice weighing between 20-30 gm were used. They were allowed food and water ad libidium upto the time of experimentation.
Each animal was used only once. All observations apomorphine induced stereotyped behavior in rats International Journal of Basic Medical Science - August 2012, Vol : 3, Issue : 3 Chandrakant Sahebrao Waghmare et al, Effect of Risperidone, An Intensity S.B.
The serotonin 5-HT receptor antagonistic activity Treatment dose (mg/kg)
‘P’ value
has been associated with efficacy against negative Mean ± SEM
symptoms of schizophrenia and a low propensity to cause extrapyramidal side effects 11,12.
The head twitch response evoked in mice occurs as a hydroxytryptamine (5-HT) neuronal systems , .
hydroxytryptophan and increases its absorption in central nervous system which in turn is converted methamphetamine induced stereotyped behavior in rats: In the present study risperidone pretreatment No. of head twitches
Treatment dose mg/kg
antagonized the head twitch activity in mice induced per 2 minutes
by 5 HTP in a dose dependent manner which shows CONCLUSION
Risperidone, the atypical antipsychotic exhibits both -Hydroxytryptophan induced head twitch activity in mice: central serotonin 5HT and dopamine D receptor antagonism and may have advantage over typical neuroleptics of a lower incidence of extrapyramidal parkinsonian medication and a tendency towards greater efficacy in controlling negative symptoms of DISCUSSION
REFERENCES
The ability of the drugs to ameliorate changes in SB induced by apomorphine or methamphetamine is a Anden NE et al; Receptor activity & turnover of standard test of potential antipsychotic activity .
dopamine and noradrenaline after neuroleptics .
Eur. J. Pharmacol.1970; 11, 303-314.
activation of postsynaptic dopamine D receptors by Carlsson A, et al; Effect of chlorpromazine or Apomorphine is believed to act directly on dopamine mouse brain. Acta Pharmaol Toxicol. 1985;20: Coook L et al; Behavioural effects of some methamphetamine induced SB in rats in a dose psychopharmacological agents. Ann. N.Y. Acad.
dependent manner which indicates that risperidone involvement with behavioural effects indicating antipsychotic activity. Eur . J. Pharmacol. 1973 International Journal of Basic Medical Science - August 2012, Vol : 3, Issue : 3 Chandrakant Sahebrao Waghmare et al, Effect of Risperidone, An Davies J A et al; The effect of anti parkinsonian serotonergic neurotransmission & negative Green AR et al; Quizapine: its effects on rat 12. Niemgeers CJE et al; Extrapyramidal symptoms brain metabolism, MAO activity and behavior.
with neuroleptics . Industrial Phramacology twitch activity in mice .Science. 1981; 30: activity in mice. Br J. Pharmacol. 1985; 735- 14. Richelson E; Serotonin mediated behaviours .
Janssen PAJ et al; Is it possible to predict the Clinical Psychiatry. 1984; 45: 331-345.
clinical effects of neuroleptic drugs from animal data? J. Pharmacol Exp. Ther. 1988; 25: 125- Psychopharmacology.1981. 74:173-178.
pretreatment on haloperidol induced catalepsy behavior-similarities & differences. Advances in and methamphetamine stereotypy in mice. Ind Biochemical Psychopharmacol. 1974; 12:241- 17. Fitton A; Risperidone –a review. Drugs. 1994; Psychopharmacology. 1992; 99: 518-527.
Professor & Head, Dept. of Pharmacology,Ashwini Rural Medical College & Hospital,Solapur. (Corresponding Author) Sachin KAssistant Professor, Dept. of Skin & V.D.,KBN Institute of Medical Sciences,Gulbarga. (Co- Author) International Journal of Basic Medical Science - August 2012, Vol : 3, Issue : 3

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