An examination of the proconvulsant actions of pyrethroid insecticides using pentylenetetrazol and amygdala kindling seizure models.
Pyrethroid insecticides have recently been purported to possess strong proconvulsant potential. The seizure-inducing properties of two pyrethroids were assessed by pentylenetetrazol (PTZ) seizure models (repeated ip, suprathreshold ip, and iv), and electrical kindling of the amygdala. The efficacy of po versus ip routes of deltamethrin administration was compared using iv-PTZ administration and tests of locomotor activity in a figure-eight maze. Both po and ip deltamethrin produced comparable decreases in motor activity indicating the effectiveness of both of these exposure routes on biological activity. The Type I pyrethroid, cismethrin (15 mg/kg, po), produced a 17% reduction in the threshold dosage of ip-PTZ required to induce a seizure, while delaying the onset of generalized seizure activity. The Type II pyrethroid, deltamethrin (10 mg/kg, po), failed to alter threshold or latency to seizure onset, but did increase seizure duration. No differences were revealed between po (0, 10, 15 mg/kg) or ip (0, 1, 10 mg/kg) administered deltamethrin on seizure thresholds or durations following iv-PTZ. Seizure severity, however, was enhanced by pyrethroids administered po in the iv-PTZ and suprathreshold-ip PTZ tests, ip deltamethrin was without effect. Cismethrin (0, 8, 15 mg/kg) and deltamethrin (0, 6, 10 mg/kg) administered po daily, 2 hours prior to electrical kindling stimulation facilitated amygdala kindling to a minimal but equivalent degree at the highest dosage. This dosage also evoked strong behavioral signs of toxicity. Deltamethrin also induced spontaneous seizures in partially kindled animals in the absence of stimulation. Thus strong evidence of proconvulsant activity of pyrethroids was not evident. The primary effects were limited to an enhancement of seizure severity in response to PTZ (tonic seizures) and the provocation of spontaneous seizures in partially kindled animals.
Gilbert
M E
ME
NSI Technology Services Corporation, Environmental Sciences, Research Triangle Park, North Carolina 27709.
Acheson
S K
SK
Mack
C M
CM
Crofton
K M
KM
D000679:Amygdala / Q000187:drug effects; D000818:Animals; D003292:Convulsants; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007306:Insecticides / Q000633:toxicity*; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009570:Nitriles; D010433:Pentylenetetrazole; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D012472:Salivation / Q000187:drug effects; D014202:Tremor / Q000139:chemically induced
D003292:Convulsants; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin; C017498:cismethrin; D010433:Pentylenetetrazole