Research article summary (published 3 Dec 2007):

CSC, an adenosine A(2A) receptor antagonist and MAO B inhibitor, reverses behavior, monoamine neurotransmission, and amino acid alterations in the 6-OHDA-lesioned rats.

Full Abstract

The present work showed the effects of 8-(-3-chlorostyryl)-caffeine (CSC), an A(2A) receptors antagonist and MAO B inhibitor, on behavior and biochemical alterations in 6-OHDA-lesioned rats. Male Wistar rats (280 g) were injected with CSC (1 and 5 mg/kg, i.p.) alone or combined with l-DOPA (50 mg/kg+benserazide 12.5 mg/kg), starting 6 days after the striatal 6-OHDA lesions, and once daily for the next 7 days. Fourteen days after the 6-OHDA lesion (and 24 h after CSC or vehicle), the number of net body rotations/h (after the apomorphine challenge) was recorded and, at the next day, animals were sacrificed. The ipsilateral striatum was used for HPLC measurements of monoamines and amino acids or for determination of nitrite contents and lipid peroxidation. Results showed that the increase in body rotation, induced by the 6-OHDA lesion, after the apomorphine challenge, was significantly and dose-dependently reversed by CSC. Furthermore, the decreased striatal levels of DA and metabolites, in the 6-OHDA-lesioned rats, were reversed after CSC treatment, and these effects were potentiated after the combination with l-DOPA. Similar results were observed with NE, 5-HT and 5-HIAA. While glutamate and GABA were increased in the 6-OHDA-lesioned group, CSC alone or mainly combined with l-DOPA reversed these alterations. In addition, the CSC treatment of 6-OHDA-lesioned rats reversed the increased nitrite formation and lipid peroxidation induced by 6-OHDA. In conclusion, CSC by means of its dual action as A(2A) antagonist and MAO-B inhibitor reversed behavior and biochemical alterations, observed in the 6-OHDA-lesioned rats, pointing out to its potential benefit for the treatment of PD.

Author information

Author/s: Aguiar, Lissiana M V (LM); Macêdo, Danielle S (DS); Vasconcelos, Silvania M M (SM); Oliveira, Aline A (AA); de Sousa, F Cléa F (FC); Viana, Glauce S B (GS);

Affiliation: Laboratory of Neuropharmacology, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, CEP 60431-970, Fortaleza, Brazil.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Brain research (Brain Res), published in Netherlands. (Language: eng)

Reference: 2008-Jan; vol 1191 (issue ) : pp 192-9

Dates: Created 2008/01/21; Completed 2008/05/19;

PMID: 18164694, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Behavior, Animal - drug effects Biogenic Monoamines - metabolism Caffeine - analogs & derivatives; pharmacology Disease Models, Animal Dose-Response Relationship, Drug Hydroxyindoleacetic Acid - metabolism Lipid Peroxidation - drug effects Male Monoamine Oxidase - drug effects Monoamine Oxidase Inhibitors - pharmacology

Neostriatum - drug effects; metabolism Neuroprotective Agents - pharmacology Nitrites - metabolism Norepinephrine - metabolism Oxidopamine Parkinson Disease - drug therapy; metabolism Rats Rats, Wistar Receptors, Adenosine A2 - agonists; metabolism Rotation Serotonin - metabolism

Associated Chemicals: Biogenic Monoamines (0) ; Monoamine Oxidase Inhibitors (0) ; Neuroprotective Agents (0) ; Nitrites (0) ; Receptors, Adenosine A2 (0) ; Oxidopamine (1199-18-4) ; 8-(3-chlorostyryl)caffeine (148589-13-3) ; Serotonin (50-67-9) ; Norepinephrine (51-41-2) ; Hydroxyindoleacetic Acid (54-16-0) ; Caffeine (58-08-2) ; Monoamine Oxidase (EC 1.4.3.4)

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