A microdialysis study of glutamate concentration in the hippocampus of rats after TsTX toxin injection and blockade of toxin effects by glutamate receptor antagonists.
Scorpion toxins act on ionic channels changing the release of neurotransmitters. In the present study, we investigated the glutamatergic release evoked by intrahippocampal injection of TsTX toxin isolated from Tityus serrulatus scorpion venom in male Wistar rats and the blockade of the toxin effect by glutamatergic antagonists. Microdialysis for neurotransmitter level quantification, electroencephalographic recording, and histopathological analysis were performed. The microdialysis method revealed enhanced levels of extracellular glutamate in the hippocampal area. The toxin injection preceded by injection of the glutamate receptor antagonists dizolcipine maleate (MK-801), D(-)2-amino-5-phosphonopentanoic acid (AP-5), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), L(+)-2-amino-3-phosphonopropionic acid (AP-3), and (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) demonstrated that MK-801 and AP-5 fully blocked the electrographic alterations and the CA1 cell loss induced by the toxin. CNQX, AP-3, and MCPG partially blocked the epileptiform discharges and no hippocampal damage was observed. Thus, we conclude that the toxin evokes glutamate release and that glutamate receptor antagonists can partially or totally block the toxin effect.
Nencioni
Ana Leonor A
AL
Laboratory of Pharmacology, Butantan Institute, Av. Dr. Vital Brasil, 1500, 05503-900 São Paulo, SP, Brazil.
Lebrun
Ivo
I
Dorce
Valquiria A C
VA
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004569:Electroencephalography / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000037:antagonists & inhibitors* / Q000633:toxicity*
D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; D012604:Scorpion Venoms; C003609:tityustoxin; D018698:Glutamic Acid