Behavioral sensitization and long-term neurochemical alterations associated with the fungicide triadimefon.
Triadimefon (TDF), a widely used triazole fungicide, blocks reuptake of the neurotransmitter dopamine (DA), similarly to cocaine. Preliminary studies show that intermittent intraperitoneal injections of TDF increase ambulatory and vertical activity across repeated injections [Neurotoxicology (in press)] leading to the hypothesis tested here, that exposure to TDF may influence the development and expression of behavioral sensitization, a model of psychostimulant-induced psychosis. Exposure of adult male C57BL/6 mice to 75 mg/kg i.p. TDF (TDF75) twice a week for 7 weeks increased vertical activity at each injection. Following a 2-week withdrawal period, a TDF challenge to test for expression of behavioral sensitization revealed further increases in vertical activity levels relative to all other conditions. TDF induction/expression of behavioral sensitization was associated with long-term, perhaps permanent modulation of dopaminergic function that included increases in striatal dihydroxyphenylacetic acid (DOPAC) and DA turnover, increases in medial prefrontal cortex (mPFC) dopamine transporter (DAT) binding, as well as decreases in DA D1 and increases in DA D2 and DAT receptor binding that appeared to target the nucleus accumbens shell (NAs) subregion. Thus, TDF exposure may serve as an environmental risk factor for DA system dysfunctions.
Reeves
Ruth
R
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. ruth_reeves@urmc.rochester.edu
Thiruchelvam
Mona
M
Richfield
Eric K
EK
Cory-Slechta
Deborah A
DA
D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D004563:Electrochemistry; D005659:Fungicides, Industrial / Q000633:toxicity*; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D014230:Triazoles / Q000633:toxicity*
D050483:Dopamine Plasma Membrane Transport Proteins; D005659:Fungicides, Industrial; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D017447:Receptors, Dopamine D1; C493215:Slc6a3 protein, mouse; D014230:Triazoles; C032910:triadimefon; D012701:Serotonin; D004298:Dopamine