Characterization of disulfoton-induced behavioral and neurochemical effects following repeated exposure.
These experiments examined the relationship between behavioral alterations and neurochemical changes in rats exposed repeatedly to disulfoton, an organophosphate cholinesterase inhibitor. Male Long-Evans rats were injected ip for 30 days with 0, 0.5, 1, or 2 mg/kg of disulfoton in corn oil. Clinical signs and motor activity were measured during the course of repeated exposure. Cognitive function, as measured in the Morris water maze, and passive avoidance procedures were assessed near the end of the dosing regimen. Regional brain acetylcholinesterase (AChE) activity was measured during the course of dosing while the total number of muscarinic receptors was measured at the end of the dosing regimen. Tolerance developed rapidly to the clinical signs produced by disulfoton, but not to the disulfoton-induced decrease in motor activity. Disulfoton affected the acquisition of water maze performance, but had no effect on passive avoidance acquisition or retention. Repeated exposure to disulfoton decreased brain AChE activity and the number of [3H]quinuclidinyl benzilate binding sites. These data indicate that, in spite of muscarinic receptor down-regulation that followed repeated exposure to disulfoton, animals become tolerant to only some of the functional effects produced by this chemical.
Llorens
J
J
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Crofton
K M
KM
Tilson
H A
HA
Ali
S F
SF
Mundy
W R
WR
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D003071:Cognition / Q000187:drug effects; D004222:Disulfoton / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004334:Drug Administration Schedule; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D014316:Tritium
D002800:Cholinesterase Inhibitors; D011976:Receptors, Muscarinic; D014316:Tritium; D004222:Disulfoton; D011813:Quinuclidinyl Benzilate