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The anticonvulsant long-term efficacy of diazepam was studied in amygdala-kindled rats. The drug was administered three times daily at doses of 5 mg/kg i.p. for 2 weeks in fully kindled animals. The severity of the kindled seizures was markedly reduced throughout the period of treatment, while tolerance developed to the effect of diazepam on seizure latency and duration and, less marked, on duration of amygdala afterdischarges. Concomitant determination of plasma concentrations of diazepam and its major metabolite, desmethyldiazepam, showed that diazepam increased during the 2 weeks of treatment, suggesting that the observed tolerance was not metabolic but functional in nature. After cessation of treatment, there was no clear indication for withdrawal symptoms except a significant increase in kindled seizure duration after 2 days. The data demonstrate that amygdala-kindled rats are a useful model to study the long-term efficacy of anticonvulsant drugs.
W Löscher, and
W S Schwark
March 1992,
European journal of pharmacology,
W Löscher, and
W S Schwark
January 1989,
Epilepsia,
W Löscher, and
W S Schwark
April 1992,
Epilepsy research,
W Löscher, and
W S Schwark
January 1992,
Pharmacology, biochemistry, and behavior,
W Löscher, and
W S Schwark
April 2000,
Experimental neurology,
W Löscher, and
W S Schwark
January 1992,
Pharmacology, biochemistry, and behavior,
W Löscher, and
W S Schwark
July 1994,
Neuropharmacology,
W Löscher, and
W S Schwark
September 1998,
Pharmacology, biochemistry, and behavior,
W Löscher, and
W S Schwark
November 1998,
Neuroscience letters,
W Löscher, and
W S Schwark
March 1998,
Epilepsy research,
