Neurochemical effects of DDT in rat brain in vivo.
p,p'-DDT and related agents act to hold the sodium channel open once opened and this effect is believed to be responsible for neurological effects of tremor and hyperexcitability in vivo. There is a good correlation between DDT-induced tremor and an increase in the levels of the metabolites of norepinephrine (NE), serotonin (5HT) and, to a lesser extent, dopamine (DA) in the brain stem (BS), hypothalamus (HYP), striatum (STR), or hippocampus (HPC). DDT also increases levels of excitatory amino acids glutamate (GLU) and aspartate (ASP), but the effect occurs only in the brain stem. These effects are dose- and time-related. Pharmacological studies found that blockade of alpha 1-adrenergic receptors attenuate DDT-induced tremor, while blockade of serotonergic, cholinergic muscarinic, and dopaminergic receptors augment the toxicity of DDT. Tremor was almost completely blocked in rats pretreated with hydantoin, an anticonvulsant believed to block repetitive firing of nerves by interfering with the inactivation gate of the sodium channel. A similar antagonism was observed for permethrin, a Type I pyrethroid believed to have a mechanism of action very similar to that of DDT. However, hydantoin increased the tremorigenic effects of chlordecone, an organochlorine whose mechanism has not been linked to the sodium channel. These data are consistent with the hypothesis that the in vivo neurotoxicity of some organochlorine insecticides is related to their effects on the sodium channel.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003634:DDT / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006827:Hydantoins / Q000633:toxicity; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000378:metabolism*; D014202:Tremor / Q000139:chemically induced
D000596:Amino Acids; D001679:Biogenic Amines; D006827:Hydantoins; D007473:Ion Channels; D012964:Sodium; D003634:DDT