Time-dependent effects of acute chlorpyrifos administration on spatial delayed alternation and cholinergic neurochemistry in weanling rats.
On postnatal day 21 (PND21), Long-Evans rat pups received a single subcutaneous injection of either 0 (corn oil vehicle), 90, 120, or 240 mg/kg chlorpyrifos and were then tested for T-maze delayed alternation on PND23 or 26. Acetylcholinesterase (AChE) activity and muscaranic receptor density [i.e., quinuclidinyl benzilate (QNB) binding] were determined in hippocampus and cortex of brains taken from pups 15 hours after the end of behavioral testing (i.e., the morning of PND24, and 27). Pups exposed to the 240 mg/kg dose of chlorpyrifos showed signs of overt toxicity that precluded behavioral testing. Exposure to the 120 mg/kg dose produced a selective memory impairment (ie., a deficit in delayed alternation but not position discrimination) relative to the 90 mg/kg and vehicle groups. This impairment was transient, however, as it appeared on PND23 and was absent by PND26. PND21 exposure to chlorpyrifos produced dose-related inhibition and recovery of brain AChE over the PND24-27 age range. A similar pattern was observed in hippocampus. Binding of [3H]QNB was reduced in frontal cortex on PND27 only at the 240 mg/kg dose. No significant effects were observed in the hippocampus. These results suggest that the neurochemical effects of acute chlorpyrifos administration are more transient, and the behavioral effects are smaller and shorter-lived than what has been reported in adult rats.
Stanton
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Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Mundy
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Ward
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Dulchinos
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Barry
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D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000254:growth & development; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D004390:Chlorpyrifos / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D008568:Memory / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects*
D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D000110:Acetylcholinesterase; D004390:Chlorpyrifos