The intent of these studies was to investigate the neural substrates activated by various panic inducing drugs. Induction of the mRNA for the proto-oncogene c-fos was used as a marker for neural activation. The alpha-2 antagonist vohimbine and cocaine both induce similar patterns of c- fos expression. c-Fos was expressed in the hippocampus, and entorhinal, pyriform and perirhinal cortices. However, expression was only seen with a seizure. Other panicogens, isoproterenol, sodium lactate, and m-CPP, that did not elicit seizures, also did not demonstrate this pattern of c- fos induction. Caffeine, however, showed a different pattern of c-fos activation where induction was very strong in the striatum at subconvulsive doses. This may be due to caffeine's adenosine antagonist properties which the other drugs lack. These data suggest that while a common neural pathway may be activated by seizures induced by some panicogenic drugs at convulsive doses, others may involve different pathways.