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Dose-related effects of clozapine and risperidone on the pattern of brain regional serotonin and dopamine metabolism and on tests related to extrapyramidal functions in rats.
Acta Pharm 2010; 60(2):129-40AP

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, significantly (p < 0.01) increased 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, significantly (p < 0.01) decreased 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 receptors interaction is involved in lower incidence of extrapyramidal side effects. Role of 5-HT1A receptors in the treatment of schizophrenia is discussed.

Authors+Show Affiliations

Neurochemistry and Biochemical Neuropharmacology Research Laboratory, Department of Biochemistry, University of Karachi, Karachi-75270, Pakistan. batool@uok.edu.pkNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21134850

Citation

Batool, Farhat, et al. "Dose-related Effects of Clozapine and Risperidone On the Pattern of Brain Regional Serotonin and Dopamine Metabolism and On Tests Related to Extrapyramidal Functions in Rats." Acta Pharmaceutica (Zagreb, Croatia), vol. 60, no. 2, 2010, pp. 129-40.
Batool F, Hasnat A, Haleem MA, et al. Dose-related effects of clozapine and risperidone on the pattern of brain regional serotonin and dopamine metabolism and on tests related to extrapyramidal functions in rats. Acta Pharm. 2010;60(2):129-40.
Batool, F., Hasnat, A., Haleem, M. A., & Haleem, D. J. (2010). Dose-related effects of clozapine and risperidone on the pattern of brain regional serotonin and dopamine metabolism and on tests related to extrapyramidal functions in rats. Acta Pharmaceutica (Zagreb, Croatia), 60(2), pp. 129-40. doi:10.2478/v1007-010-0014-y.
Batool F, et al. Dose-related Effects of Clozapine and Risperidone On the Pattern of Brain Regional Serotonin and Dopamine Metabolism and On Tests Related to Extrapyramidal Functions in Rats. Acta Pharm. 2010;60(2):129-40. PubMed PMID: 21134850.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dose-related effects of clozapine and risperidone on the pattern of brain regional serotonin and dopamine metabolism and on tests related to extrapyramidal functions in rats. AU - Batool,Farhat, AU - Hasnat,Ambreen, AU - Haleem,Muhammad Abdul, AU - Haleem,Darakhshan Jabeen, PY - 2010/12/8/entrez PY - 2010/12/8/pubmed PY - 2011/3/4/medline SP - 129 EP - 40 JF - Acta pharmaceutica (Zagreb, Croatia) JO - Acta Pharm VL - 60 IS - 2 N2 - 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, significantly (p < 0.01) increased 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, significantly (p < 0.01) decreased 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 receptors interaction is involved in lower incidence of extrapyramidal side effects. Role of 5-HT1A receptors in the treatment of schizophrenia is discussed. SN - 1846-9558 UR - https://www.unboundmedicine.com/medline/citation/21134850/Dose_related_effects_of_clozapine_and_risperidone_on_the_pattern_of_brain_regional_serotonin_and_dopamine_metabolism_and_on_tests_related_to_extrapyramidal_functions_in_rats_ L2 - https://www.degruyter.com/doi/10.2478/v1007-010-0014-y DB - PRIME DP - Unbound Medicine ER -