Characteristics of the prolonged inhibition produced by a range of pyrethroids in the rat hippocampus.
Eight different synthetic pyrethroids were examined to determine their effects on the excitability of hippocampal granule cells in urethane-anesthetized rats. A paired stimulus approach was used. All eight prolonged the depression of granule cell excitability that follows stimulation of their major synaptic input, the perforant path. The magnitude of this effect depended upon the class to which the pyrethroid belonged. Type I pyrethroids (those primarily producing tremor) prolonged the depression of granule cell excitability for shorter periods than did type II pyrethroids (those primarily producing salivation and choreoathetosis) or pyrethroids producing a mixed type of intoxication. No overlap was found between groups. To determine whether the difference observed between type I and type II pyrethroids was the result of an infelicitous selection of doses, cismethrin (type I) was tested over a dose range of 1.5-24 times the conscious rat iv LD50. Even at the highest dose, the prolongation remained well below that produced by type II pyrethroids. The effect of deltamethrin was shown to be consistent with the production or potentiation of a surmountable inhibitory response. This action of deltamethrin was antagonizable by mephenesin and lidocaine, but not by picrotoxin or halothane. The type of effect, its time course, and the antagonism data suggest that type II pyrethroids enhance inhibition in the dentate gyrus. This action does not appear to be mediated by GABAA receptors.
Joy
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RM
Department of Veterinary Pharmacology and Toxicology, School of Veterinary Medicine, University of California, Davis 95616.
Lister
T
T
Ray
D E
DE
Seville
M P
MP
D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007306:Insecticides / Q000633:toxicity; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D009570:Nitriles; D010852:Picrotoxin / Q000494:pharmacology; D011722:Pyrethrins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D013997:Time Factors
D007306:Insecticides; D008012:Lidocaine; D009570:Nitriles; D010852:Picrotoxin; D011722:Pyrethrins; C017180:decamethrin