Threshold Tonic Extension Test
Threshold tonic extension (TTE) test is a nonselective, electroconvulsive seizure model that is usually used only with those compounds that are inactive in the MES and scMET tests. Twenty mice are pretreated i.p. with 100 mg/kg of the test substance, less if Test 1 indicates toxicity at that level. Groups of 4 animals each are tested at 1/4, 1/2, 1, 2 and 4 hr after treatment and are challenged with the CC97 for TTE (12.5 mA for 0.2 sec) delivered through corneal electrodes to elicit a threshold tonic extension seizure. Mice not displaying a hindlimb tonic extension are considered protected. The ability of a test substance to block TTE seizures is quantified by varying the doses between that which protects 100% of mice and that which protects 0% and calculating an ED50 by probit analysis. This test is no longer run routinely in the ETSP.