Methyl parathion increases neuronal activities in the rat locus coeruleus.
Exposure to organophosphate insecticides induces undesirable behavioral changes in humans, including anxiety and irritability, depression, cognitive disturbances and sleep disorders. Little information currently exists concerning the neural mechanisms underlying such behavioral changes. The brain stem locus coeruleus (LC) could be a mediator of organophosphate insecticide-induced behavioral toxicities since it contains high levels of acetylcholinesterase and is involved in the regulation of the sleep-wake cycle, attention, arousal, memory, and pathological processes, including anxiety and depression. In the present study, using a multi-wire recording technique, we examined the effects of methyl parathion, a commonly used organophosphate insecticide, on the firing patterns of LC neurons in rats. Systemic administration of a single dose of methyl parathion (1 mg/kg, i.v.) increased the spontaneous firing rates of LC neurons by 240% but did not change the temporal relationships among the activities of multiple LC neurons. This dose of methyl parathion induced a 50% decrease in blood acetylcholinesterase activity and a 48% decrease in LC acetylcholinesterase activity. The methyl parathion-induced excitation of LC neurons was reversed by administration of atropine sulfate, a muscarinic receptor antagonist, indicating an involvement of muscarinic receptors. The methyl parathion-induced increase in LC neuronal activity returned to normal within 30 min while the blood acetylcholinesterase activity remained inhibited for over 1 h. These data indicate that methyl parathion treatment can elicit excitation of LC neurons. Such excitation could contribute to the neuronal basis of organophosphate insecticide-induced behavioral changes in human.
Zhu
Hong
H
Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, Jackson, Miss. 39216, USA. hozhu@ent.umsmed.edu
Zhou
Wu
W
Li
Xiao R
XR
Ma
Tangen
T
Ho
Ing K
IK
Rockhold
Robin W
RW
D000110:Acetylcholinesterase / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004594:Electrophysiology; D008125:Locus Coeruleus / Q000187:drug effects*; D008297:Male; D008743:Methyl Parathion / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D008743:Methyl Parathion; D000110:Acetylcholinesterase