Behavioral effects and neuroanatomical targets of acute atrazine exposure in the male Sprague-Dawley rat

• Published in: Neurotoxicology (Park Forest South) 2017-01, Vol.58, p.161-170
• Main Authors: Rodriguez, V.M., Mendoza-Trejo, M.S., Hernandez-Plata, I., Giordano, M.
• Format: Article
• Language: English
• Subjects: Amygdala; Analysis of Variance; Anatomy; Animals; Atrazine; Atrazine - pharmacology; Basal ganglia; Body weight; Brain; Brain - cytology; Brain - drug effects; Brain - metabolism; Brain architecture; Brain mapping; c-Fos; c-Fos protein; Cell activation; Cellulose; Chromatography; Corn; Dopamine; Dopamine receptors; Dose-Response Relationship, Drug; Experiments; Exposure; Forebrain; Fuel consumption; GABA; gamma-Aminobutyric Acid - metabolism; Ganglia; Glutamate; Glutamic Acid - metabolism; Herbicides; Herbicides - pharmacology; High performance liquid chromatography; Hindbrain; Hydroxylase; Immunohistochemistry; Injection; Liquid chromatography; Locomotion - drug effects; Locomotor activity; Male; Neurotoxicity; Nuclei (cytology); Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Sprague-Dawley; Rodents; Sorghum; Statistical analysis; Superior colliculus; Thalamus; Tyrosine; Tyrosine 3-Monooxygenase - metabolism; Weed control; γ-Aminobutyric acid
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2016.12.006

•Ninety minutes after exposure to ATR (100mg/kg BW) spontaneous locomotor activity is reduced.•ATR (100mg/kg BW) increases c-Fos expression in thalamus, central amygdala, subthalamic nucleus, superior colliculus, and substantia nigra.•Tyrosine hydroxylase- positive cells were not selectively activated by ATR.•Acute exposure to ATR (100mg/kg BW) does not affect tissue levels of GABA or glutamate in brain regions with high levels of these transmitters.•The effects of ATR on locomotor activity were partially reversed by a GABA-B antagonist. Atrazine (ATR) is an herbicide broadly used in the world to control weeds in corn and sorghum fields, and it is potentially toxic for the dopaminergic system. Alterations in dopaminergic markers after ATR administration in rats and C57BL/6 mice have been reported. Behaviorally, it has been observed that ATR exposure causes hypoactivity shortly after its administration. To understand how acute ATR administration induces hypoactivity, we set out to map the brain areas responsive to ATR using c-Fos as a marker of neuronal activity, and tyrosine hydroxylase (TH) as a marker of dopaminergic neurons. The levels of glutamate and gamma-aminobutyric acid (GABA) were measured using high performance liquid chromatography, and spontaneous locomotor activity was evaluated as well. Male Sprague-Dawley rats received a systemic injection of 1% methyl cellulose (vehicle) or 100mg ATR/kg body weight to evaluate locomotor activity immediately after injection, c-Fos and TH immunohistochemistry in forebrain, midbrain and hindbrain, or glutamate and GABA content in various brain areas 90min after injection. To assess the possible involvement of the GABAergic system on ATR effects we tested the effects of a GABA-B antagonist. We found statistically significant decreases in locomotor activity, which were partially reversed by the GABA-B antagonist, and increases in the number of c-Fos-positive cells in thalamus, central amygdala, subthalamic nucleus, superior colliculus, and substantia nigra, TH positive cells were not selectively activated by ATR. The acute administration of ATR did not affect GABA or glutamate tissue levels but significantly decreased locomotor activity. These results corroborate the hypoactivity-inducing effect of ATR, and show that non-dopaminergic cells respond to the acute administration of ATR. The activation of cell populations in the basal ganglia and their target nuclei may contribute to the acute behavioral effects of