Failure of chronic treatment with abecarnil to induce contigent and noncontingent tolerance in pentylenetetrazol-kindled rats.
We examined the effect of chronic treatment with abecarnil, a selective agonist at gamma-aminobutyric acid(A) (GABA(A)) receptors, on the development of tolerance to its anticonvulsant effect in pentylenetetrazole (PTZ)-kindled rats. We used two different experimental protocols to differentiate between pharmacological (noncontingent) and contingent tolerance. In one group of animals, kindling was suspended and abercarnil (1mg/kg intraperitoneally, i.p.) was administered three times daily for 15 days. In a second group of rats, PTZ-kindling was continued during chronic treatment with abecarnil. Tolerance to the anticonvulsant effect of a subsequent challenge dose of abecarnil (0.5 mg/kg i.p.) did not develop in either experimental group.
Serra
M
M
Department of experimental Biology "B. Loddo," University of Cagliari, Italy.
Ghiani
C A
CA
Maciocco
E
E
Pisu
M G
MG
Tuligi
G
G
Porceddu
M L
ML
Giggio
G
G
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D002243:Carbolines / Q000494:pharmacology* / Q000627:therapeutic use; D004361:Drug Tolerance; D004827:Epilepsy / Q000188:drug therapy / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects
D000927:Anticonvulsants; D002243:Carbolines; D018079:Receptors, GABA; C062769:abecarnil; D010433:Pentylenetetrazole