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Sci. Pharm. 2010, 78(2), 259-274; doi:10.3797/scipharm.0907-20

Acute Administration of Clozapine and Risperidone Altered Dopamine Metabolism More in Rat Caudate than in Nucleus Accumbens: A Dose-Response Relationship

1
Neurochemistry and Biochemical Neuropharmacology Research Laboratory, Dept of Biochemistry, University of Karachi, Karachi-75270, Pakistan
2
Dept of Biomedical Engineering, Sir Syed University of Engineering and Technology, Karachi, Pakistan
*
Author to whom correspondence should be addressed.
Received: 20 August 2009 / Accepted: 26 November 2009 / Published: 29 November 2009
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Abstract

The present study compares the extrapyramidal and neurochemical effects of clozapine and risperidone in rat caudate (corpus striatum) and nucleus accumbens (ventral striatum) dose-dependently. Animals injected with clozapine (2.5, 5.0 and 10.0 mg/kg IP) or risperidone (1.0, 2.5 and 5.0 mg/kg IP) in acute were sacrificed 1 h later to collect brain samples. Extrapyramidal side effects (EPS) in terms of locomotor activity and catalepsy were monitored in each animal after the drug or vehicle administration. Maximum cataleptic potentials were found only at high doses of clozapine (10.0 mg/kg; 60%) and risperidone (5.0 mg/kg; 100%). Neurochemical estimations were carried out by HPLC-EC. Both drugs at all doses significantly (p<0.01) increased the concentration of homovanillic acid (HVA), a metabolite of DA, in the caudate nucleus and decreased in nucleus accumbens. Levels of Dihydroxyphenylacetic acid (DOPAC) significantly (p<0.01) increased in the caudate by clozapine administration and decreased in the nucleus accumbens by the administration of both drugs in a dose-dependent manner. 5-Hydroxyindoleacetic acid (5-HIAA), the predominant metabolite of serotonin significantly decreased in the caudate and nucleus accumbens in a similar fashion. Levels of tryptophan (TRP) were remained insignificant in caudate and nucleus accumbens by the injections of two drugs. In caudate, clozapine and risperidone administrations significantly (p<0.01) decreased HVA/DA ratio and increased DOPAC/DA ratio in nucleus accumbens at all doses. The findings suggest the evidence for DA/5-HT receptor interaction as an important link in the lower incidence of EPS. The possible role of serotonin1A receptors in the pathophysiology of schizophrenia is also discussed.
Keywords: Atypical antipsychotics; Extrapyramidal side effects; Dopamine D2 receptors; Serotonin1A receptors; Schizophrenia Atypical antipsychotics; Extrapyramidal side effects; Dopamine D2 receptors; Serotonin1A receptors; Schizophrenia
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

BATOOL, F.; HALEEM, M.A.; HALEEM, D.J. Acute Administration of Clozapine and Risperidone Altered Dopamine Metabolism More in Rat Caudate than in Nucleus Accumbens: A Dose-Response Relationship. Sci. Pharm. 2010, 78, 259-274.

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