Pyrethroids and enhanced inhibition in the hippocampus of the rat.
The pyrethroid insecticides have been divided into two classes on the basis of their biochemical actions and behavioral indices of toxicity. Both types of pyrethroids have effects on sodium conductance, and Type II pyrethroids have been reported to antagonize gamma-aminobutyric acid (GABA) by interacting with the t-butyl-bicyclophosphorothionate (TBPS)/picrotoxinin binding site. The dentate gyrus of the hippocampus is equipped with GABAergic recurrent inhibitory circuits. The present experiment was designed to demonstrate dissociation in the biochemistry of pyrethroids by activating the perforant path with pairs of stimulus pulses and monitoring the recurrent inhibition in this circuit. Antagonism of GABA leads to a reduction in inhibition, measured as an increase in the size of the population spike in response to the second pulse of the pair. The GABAergic properties of the pyrethroids were assessed by examining paired pulse inhibition before and after oral treatment with 20 mg/kg of cismethrin (Type I), 20 mg/kg of fenvalerate, or 10 mg/kg of deltamethrin (Type IIs). Input/output (I/O) functions revealed a reduction in excitatory postsynaptic potential (EPSP) following cismethrin and deltamethrin. Population spike height was unaffected. Fenvalerate had no effect on I/O functions. In contrast to the prediction of reduced inhibition following treatment with Type II pyrethroids, deltamethrin and fenvalerate increased inhibition up to 500 and 150 ms interpulse intervals, respectively. Cismethrin was without effect on paired pulse inhibition. These findings fail to provide evidence of GABA antagonistic properties of Type II pyrethroids and may be best explained by a differential effect of these three pyrethroids on sodium channel kinetics.
Gilbert
M E
ME
NSI-Environmental Sciences, Research Triangle Park, NC 27709.
Mack
C M
CM
Crofton
K M
KM
D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007306:Insecticides / Q000494:pharmacology*; D008297:Male; D009570:Nitriles; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D012016:Reference Values; D013329:Structure-Activity Relationship; D013569:Synapses / Q000502:physiology
D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin; C017498:cismethrin; C017690:fenvalerate