title: Repeated exposure to the herbicide atrazine alters locomotor activity and the nigrostriatal dopaminergic system of the albino rat.
abstract: Atrazine (ATR) is used as a pre- and post-emergent herbicide; although banned in several countries of the European Community, it is still used extensively around the world. A recent study in rats has shown that chronic, daily exposure to 10 mg ATR/kg BW causes hyperactivity, disrupts motor coordination and learning of behavioral tasks, and decreases dopamine levels in the brain. In order to evaluate the short-term effect of ATR exposure on locomotor activity, monoamine markers, and antioxidants, adult male Sprague-Dawley rats received six IP injections of 100 mg ATR/kg BW or vehicle over two weeks. After every ATR injection we found hypoactivity that lasted up to five days, and it was accompanied by reductions in levels of striatal DA, DOPAC, and HVA without any alteration in the striatal expression of the mRNAs for Mn-SOD, Trx-1, DAR-D(1), or DAR-D(2). In contrast, in the nucleus accumbens no changes in monoamine markers were observed, and a down-regulation of Trx-1 expression was detected shortly after the ATR treatment. Moreover, in the ventral midbrain, we found that ATR induced a down-regulation of mRNA for Th and DAT, but it increased VMAT2 mRNA expression. Decreases of monoamine levels and of locomotor activity disappeared three months after ATR treatment; however, an amphetamine challenge (1 mg/kg) given two months after the ATR treatment resulted in a significant stimulation in the exposed group, revealing hidden effects of ATR on dopaminergic systems. These results indicate that ATR exposure differentially modifies the dopaminergic systems, and these modifications may underlie the behavioral changes observed.
authors.affiliation: Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Querétaro, Querétaro 76230, Mexico. vermire@yahoo.com
authors.forename: Verónica M
authors.initials: VM
authors.lastname: Rodríguez
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Limón-Pacheco
authors.forename: Maria Soledad
authors.initials: MS
authors.lastname: Mendoza-Trejo
authors.forename: Adriana
authors.initials: A
authors.lastname: González-Gallardo
authors.forename: Isela
authors.initials: I
authors.lastname: Hernández-Plata
authors.forename: Magda
authors.initials: M
authors.lastname: Giordano
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000417:Albinism / Q000235:genetics; D000818:Animals; D001280:Atrazine / Q000008:administration & dosage / Q000633:toxicity*; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D004334:Drug Administration Schedule; D005106:Exploratory Behavior / Q000187:drug effects; D006540:Herbicides / Q000008:administration & dosage / Q000633:toxicity*; D006719:Homovanillic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D006540:Herbicides; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C493454:Slc18a2 protein, rat; C495697:Txn1 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D013879:Thioredoxins; D014446:Tyrosine 3-Monooxygenase; D013482:Superoxide Dismutase; D001280:Atrazine; D004298:Dopamine; D006719:Homovanillic Acid