Original scientific paper

https://doi.org/10.2478/v10007-010-0014-y

Dose-related effects of clozapine and risperidone on pattern of brain regional serotonin and dopamine metabolism and on extrapyramidal functions in rats

Farhat Batool ; Neurochemistry and Biochemical Neuropharmacology Research Laboratory, Department of Biochemistry, University of Karachi, Karachi-75270, Pakistan
Ambreen Hasnat ; Neurochemistry and Biochemical Neuropharmacology Research Laboratory, Department of Biochemistry, University of Karachi, Karachi-75270, Pakistan
Muhammad Abdul Haleem ; Department of Biomedical Engineering, Sir Syed University of Engineering, and Technology, Karachi, Pakistan
Darakhshan Jabeen Haleem ; Neurochemistry and Biochemical Neuropharmacology Research Laboratory, Department of Biochemistry, University of Karachi, Karachi-75270, Pakistan

Abstract

The present study was designed to evaluate the behavioral and neurochemical profiles of clozapine and risperidone in rats in a dose-dependent manner. Animals injected intraperitoneally (i.p.) with clozapine (2.5, 5.0 and 10.0 mg kg1) or risperidone (1.0, 2.5 and 5.0 mg kg1) were sacrificed 1 h later to collect brain samples. Hypolocomotive effects (home cage activity and catalepsy) were successively monitored in each animal after the drug or saline administration. Both drugs significantly (p < 0.01) decreased locomotor activity at high doses and in a dose-dependent manner. Maximum (100 %) cataleptic potential was achieved at a high dose (5.0 mg kg1) of risperidone. Neurochemical estimations were carried out by HPLC with electrochemical detection. Both drugs, at all doses, increased significantly (p < 0.01) the concentration of homovanillic acid (HVA), a metabolite of dopamine (DA), in the striatum. Dihydroxyphenylacetic acid (DOPAC) levels increased in the striatum and decreased in the rest of the brain, particularly in clozapine-injected rats. 5-Hydroxyindoleacetic acid (5-HIAA), the predominant metabolite of serotonin, decreased significantly (p < 0.01) in the striatum. 5-Hydroxytryptamine (5-HT) was significantly (p < 0.01) increased by risperidone and decreased by clozapine in the rest of the brain. Striatal tryptophan (TRP) was significantly (p < 0.01) decreased by risperidone and increased in the rest of the brain. The striatal HVA/DA ratio increased and the 5-HT turnover rate remained unchanged in the rest of the brain. Results suggest that the affinity of the two drugs towards D2/5-HT1A receptor interaction is involved in lower incidence of extrapyramidal side effects. Role of 5-HT1A receptors in the treatment of schizophrenia is discussed.

Keywords

atypical antipsychotics; dopamine D2 receptors; extrapyramidal side effects, serotonin1A receptors; schizophrenia

Hrčak ID:

48384

URI

https://hrcak.srce.hr/48384

Publication date:

1.6.2010.

Article data in other languages: croatian

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