Interactions of GABAA antagonists with deltamethrin, diazepam, pentobarbital, and SKF100330A in the rat dentate gyrus.
Activation of dentate gyrus granule cells leads to a period of depressed excitability mediated primarily by recurrent inhibition. This response can be increased in intensity and duration by drugs that enhance GABAA-mediated inhibition including GABA uptake blockers (SKF100330A), benzodiazepines (diazepam), and barbiturates (pentobarbital). It can be attenuated or abolished by administration of the GABAA antagonists picrotoxin and bicuculline. Type II pyrethroids, such as deltamethrin, produce effects in vitro which lead one to expect that they would decrease GABA-mediated inhibition. However, administration of deltamethrin to animals intensifies the inhibitory consequences of granule cell activation by many fold. To determine the role of GABAA-mediated mechanisms in the action of deltamethrin, we have looked at its antagonism by bicuculline and picrotoxin. Neither GABAA antagonist reduced the duration of the inhibition produced by deltamethrin. The only effect observed was a small but significant reduction in intensity of inhibition during the period of 10-40 msec after activation of the granule cells. For comparative purposes we have also examined the antagonism produced by bicuculline and picrotoxin on agents known to enhance GABAA-mediated inhibition. These antagonists were quite effective in antagonizing the enhancement of inhibition produced by diazepam and SKF 100330A. Bicuculline was also effective in antagonizing pentobarbital while picrotoxin was not. These results suggest that the prolongation of inhibition produced by deltamethrin in dentate granule cells does not result simply from an extension of GABAA-mediated inhibition, but rather derives from a different source.
Joy
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RM
Department of Veterinary Pharmacology and Toxicology, School of Veterinary Medicine, University of California, Davis 95616.
Albertson
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TE
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003975:Diazepam / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D018756:GABA Antagonists; D006624:Hippocampus / Q000187:drug effects*; D007306:Insecticides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009539:Nicotinic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009570:Nitriles; D010424:Pentobarbital / Q000494:pharmacology*; D010852:Picrotoxin / Q000494:pharmacology; D011722:Pyrethrins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000927:Anticonvulsants; D001640:Bicuculline; D003975:Diazepam; D018756:GABA Antagonists; D007306:Insecticides; D009539:Nicotinic Acids; D009570:Nitriles; D010424:Pentobarbital; D010852:Picrotoxin; D011722:Pyrethrins; C017180:decamethrin; C045597:SK&F 100330-A