Repeated exposure to the herbicide atrazine alters locomotor activity and the nigrostriatal dopaminergic system of the albino rat

• Published in: Neurotoxicology (Park Forest South) Vol. 34; pp. 82 - 94
• Main Authors: Rodríguez, Verónica M., Limón-Pacheco, Jorge H., Mendoza-Trejo, Maria Soledad, González-Gallardo, Adriana, Hernández-Plata, Isela, Giordano, Magda
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.01.2013; Elsevier
• Subjects: 3,4-Dihydroxyphenylacetic Acid - metabolism; Albinism - genetics; Animals; Antioxidants; Atrazine - administration & dosage; Atrazine - toxicity; Basal Ganglia - drug effects; Basal Ganglia - metabolism; Basal Ganglia - physiopathology; Behavior, Animal - drug effects; Biological and medical sciences; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins - genetics; Dopamine Plasma Membrane Transport Proteins - metabolism; Dopamine receptors; Dopamine transporter; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Drug Administration Schedule; Exploratory Behavior - drug effects; Herbicides; Herbicides - administration & dosage; Herbicides - toxicity; Homovanillic Acid - metabolism; Injections, Intraperitoneal; Male; Medical sciences; Motor Activity - drug effects; Pesticides, fertilizers and other agrochemicals toxicology; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1 - genetics; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D2 - metabolism; RNA, Messenger - metabolism; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Substantia Nigra - physiopathology; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Thioredoxins - genetics; Thioredoxins - metabolism; Time Factors; Toxicology; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism; Tyrosine hydroxylase; Vesicular Monoamine Transport Proteins - genetics; Vesicular Monoamine Transport Proteins - metabolism; Vesicular monoamine transporter 2; Antioxidants; Herbicides; Dopamine transporter; Tyrosine hydroxylase; Vesicular monoamine transporter 2; Dopamine receptors; Rat; Toxicity; Tyrosine 3-monooxygenase; Multiple dose; Motricity; Vesicular monoamine transporter; Enzyme; Dopamine receptor; Pesticides; Rodentia; Antioxidant; Herbicide; Locomotion; Vertebrata; Mammalia; Animal; Triazine derivatives; Oxidoreductases; Atrazine
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2012.10.012

► ATR injections decreased locomotor activity after every administration. ► ATR induced a short-lasting hypoactivity that disappeared 10 days later. ► Persisting changes on the DAergic system were revealed with an amphetamine challenge. ► ATR induced a short-lasting decrease in striatal monoamine levels. ► ATR induced a down-regulation of mRNA for Th and DAT and increased VMAT2 mRNA expression. 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 10mgATR/kgBW 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 100mgATR/kgBW 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-D1, or DAR-D2. 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 (1mg/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.