Studies investigating the neural substrates of various panic inducing drugs have been initiated. Induction of the mRNA for the proto-oncogene c-fos is being used as a marker for neural activation. Similarities and differences of the neuroanatomical pattern of c-fos activation between the panicogens is being examined. The alpha-2 antagonist yohimbine and cocaine both induce similar patterns of c-fos induction. c-fos is expressed in the hippocampus and entorhinal and perirhinal cortices. Other panicogens isoproterenol and m-CPP do not demonstrate this pattern of c-fos induction. Furthermore, caffeine shows a highly differential pattern of c-fos activation where induction is very strong in the striatum. The data suggest that a variety of neural pathways may be activated by panicogenic drugs.