Ashdin Publishing Journal of Drug and Alcohol Research Vol. 4 (2015), Article ID 235959, 5 pages doi:10.4303/jdar/235959 ASHDIN publishing Research Article Protective Effects of Caffeic Acid on Quinolinic Acid-Induced Behavioral and Oxidative Alterations in Rats Ana Laura Col´ ın-Gonz´ alez, 1 Sayde S´ anchez-Hern´ andez, 1 Maria Eduarda de Lima, 2 Syed F. Ali, 3 Anah´ ı Chavarr´ ıa, 4 Juana Villeda, 5 and Abel Santamar´ ıa 1 1 Laboratorio de Amino´ acidos Excitadores, Instituto Nacional de Neurolog´ ıa y Neurocirug´ ıa, Mexico City 14269, Mexico 2 Universidade Federal do Pampa, Uruguaiana, Brazil 3 Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA 4 Unidad de Medicina Experimental, Facultad de Medicina, Universidad Nacional Aut´ onoma de M´ exico, Mexico City 04510, Mexico 5 Laboratorio de Patolog´ ıa Experimental, Instituto Nacional de Neurolog´ ıa y Neurocirug´ ıa, Mexico City 14269, Mexico Address correspondence to Abel Santamar´ ıa, absada@yahoo.com Received 30 October 2015; Revised 20 November 2015; Accepted 9 December 2015 Copyright © 2015 Ana Laura Col´ ın-Gonz´ alez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Study design. The protective effects of the natural antiox- idant caffeic acid (CA) on behavioral tasks and lipid peroxidation were tested in an excitotoxic model produced by unilateral intrastriatal injection of quinolinic acid (QUIN), and in striatal slices incubated in the presence of the same toxin. CA (20 mg/kg) was administered intraperitoneally to rats every day for five days; then, rats received QUIN (240 nmol/μL). Six days later, motor asymmetry was quantified by the preferential use of forelimbs and the circling behavior tests. Rat striatal slices (300 μm thick) were incubated in the presence of CA (30–300 μM) and/or QUIN (100 μM) to estimate oxidative stress. Results. QUIN induced motor asymmetry in lesioned rats and increased lipid peroxidation in striatal slices when compared to control values. CA prevented the QUIN-induced toxic endpoints in a concentration- dependent manner. Conclusion. Our results support the neuroprotective role of CA in neurotoxic paradigms recruiting excitotoxic events. Keywords motor asymmetry; antioxidant defense; excitotoxicity; oxidative stress; corpus striatum; caffeic acid; quinolinic acid 1. Introduction The kynurenine pathway for tryptophan degradation is responsible for the formation of neuroactive metabolites in the CNS [1]. The alteration in the levels of these metabolites is involved in different neurological disorders [2]. One of these metabolites is quinolinic acid (QUIN), a glutamate agonist acting on NMDA receptors (NMDAr) [3]. Through excitotoxic events, QUIN induces oxidative stress, increased intracellular Ca 2+ levels, enhanced levels of extracellular glutamate, augmented protease activity, and stimulated deadly cascades under different experimental conditions [4, 5]. In turn, excitotoxicity can be defined as a toxic mecha- nism affecting neurons that are continuously stimulated via overactivation of NMDAr and further increased intracellular Ca 2+ levels triggering deadly cascades [6]. Caffeic acid (3,4-dihydroxycinnamic acid or CA) is a natural phenolic compound that has been shown to exert neuroprotective actions against different neurotoxic insults, (a) (b) Figure 1: Schematic representation of the chemical struc- tures of QUIN (a) and CA (b). including ischemia and excitotoxic damage in rodents, and these effects have been related with its antioxidant and anti- inflammatory properties [7, 8, 9, 10]. Although some positive effects of CA on endpoints of behavioral (motor activity) and redox status (reduced glutathione/oxidized glutathione) alterations in the excitotoxic model induced by QUIN in rats have already been reported [9], key behavioral and oxidative stress markers denoting neuroprotection are still needed as complementary evidence. In particular for this toxic model, motor asymmetry and lipid peroxidation as an index of oxidative damage in the striatum are required. Therefore, the present study aims to evaluate the effects of CA on QUIN-induced behavioral and biochemical alterations in the rat brain. For comparative purposes, the effect of CA was also tested in the 3-nitropropionic acid (3-NP) model of striatal toxicity. The chemical structures of both CA and QUIN are represented in Figure 1. 2. Materials and methods 2.1. Reagents Apomorphine, CA, QUIN, 3-NP, thiobarbituric acid (TBA), and other reagents were obtained from Sigma-Aldrich