Genetically Slow (GSAK) and Fast (GFAK) Amygdala Kindling Rats Exhibit Differential Lethality at Intravenous Cocaine Seizure Threshold

Objective. This study was conducted to determine if GFAK rats possessed lower intravenous cocaine seizure thresholds than GSAK rats. Background. Cocaine seizures originate in the amygdala. GFAK rats were bred from an F1 cross of Wistar and Long Evans rats to exhibit rapid amygdala kindling. GSAK rats were bred to exhibit slow amygdala kindling. Methods. Rats were implanted with chronic silastic catheters under ketamine/xylazine anesthesia (70 mg/kg; 6 mg/kg IP). Cocaine was infused at 10mg/kg/min in a volume of 1 ml/min to the onset of seizure and stopped. Incidence of lethality was noted. Cocaine seizure thresholds were determined in GFAK and GSAK rats. Subsequently, cocaine seizure thresholds were determined in Wistar, Long- Evans and Sprague-Dawley rats. Results. Cocaine seizure thresholds were lower in GSAK (7.1 + 0.4 mg/kg) than GFAK (8.6 mg/kg + 0.5 mg/kg) rats. One hundred percent of the GSAK rats died at seizure threshold compared to only 16.7 percent of the GFAK rats. Wistar, Long-Evans and Sprague-Dawley rats did not differ in intravenous cocaine seizure threshold. However, 27.3 percent of the Wistar rats died at cocaine seizure threshold. None of the Long-Evans or Sprague-Dawley rats died at cocaine seizure threshold. Conclusion. The unique sensitivity of the GSAK rats to the lethal effects of cocaine appears to have been inherited from its Wistar progenitors. Selective breeding for resistance to amygdala kindling concomitantly resulted in sensitivity to cocaine lethality. Grants. This study was supported in part by NS 28118.