Abstracts

Methamphetamine (METH) is a popular drug of abuse and in high doses causes toxicity and neuronal degeneration. These effects are link to many cases of METH-induced seizures observed at emergency rooms. The present study was aimed to see if wheather METH-treated animals are at increased risk for further seizure susceptibility. The present study evaluated the effect of acute METH in two well establishes models; 6-Hertz psychomotor seizures (6-Hertz) and Threshold Tonic Extension Seizures(TTE). Male Sprague-Dawley albino rats (80-100g) obtained from Charles Rivers laboratories were treated with METH four doses (10 mg/kg subcutaneously at 2 hour/intervals). At 1 and 24 hours after METH administration the median and current required to produce a 6 Hz or Tonic Extension seizure was established using the staircase procedure. Convulsive current response curves were generated, CC50 values and 95% confidence intervals calculated using MINITAB. METH treatment reduced the seizure threshold for 6 Hz seizures for example at 1 hour the calculated CC50 was 57 mA vs 76 mA and at 24 hours the calculated CC50 was 69 mA vs 82 mA for METH vs vehicle respectively. Interestingly, acute METH cause a marked increase in Tonic extension seizure at 1 hour 87 mA vs 36 mA for METH vs vehicle respectively. This difference was gone by 24 hours. The findings suggest that paradoxical effects of METH on seizure threshold in two different seizure models (e.i.) 6 Hz and TTE could be due to different seizure threshold and propagation. Investigations are atempting elucidate the underlying mechanisms of action of METH. (Supported by NIDA grant 5-PO1-DA 13367-04.)