transgene that can be detected as nuclear (3-galactosidase activity. For 
example, both PTZ and kainic acid seizures evoke a widespread, transient 
induction of the transgene in overlapping, but not identical, populations of 
neurons. These differences in distribution were not so apparent when studied 
by Fos immunohistochemistry since the antibodies react with related proteins 
that are induced to high levels over protracted periods following seizure 
(Morgan et al. 1987; Sonnenberg et al. 1989a, 1989c). The transgene product, 
like Fos, has a relatively short half-life, and so a precise map of Fos expression 
is obtained. This has also pointed to the surprising fact that, in some neurons, 
Fos-like proteins must be induced with little or no Fos expression. That 
differences in patterns of Fos induction exist between related stimuli should 
come as no surprise; in fact, it would be surprising if such differences did not 
exist. It has only been the lack of specificity of the reagents that has heretofore 
obscured these differences. 
Recently, the analysis of gene induction in the fos-lacZ transgenic mouse has 
been extended to examine other forms of stimulation. Light exposure during 
presumptive night will induce the transgene in the suprachiasmatic nucleus 
of the hypothalamus, as it does cognate c -fos. Thus, the transgene is capable 
of responding to a physiological stimulus. The fos-lacZ transgene is also 
responsive to drugs of abuse. In preliminary experiments both cocaine and 
amphetamines have induced the gene in caudatoputamen; however, the 
latter agent is the more efficient of the two. In addition, amphetamine, but not 
cocaine, elicits a considerable induction of the gene in other regions of the CNS 
that are presently being investigated. Therefore, future studies will be aimed at 
establishing whether the transgenic mice can be useful in the assessment of 
dependence and withdrawal in chronic models of drug abuse. 
PERSPECTIVE ON THE APPLICATION OF IE GENES IN THE STUDY OF 
DRUGS OF ABUSE 
A combination of Fos immunohistochemistry, in situ hybridization, and now 
histochemistry for p-galactosidase in transgenic mice provides a novel and 
precise method for assessing certain aspects of the physiology of drugs of 
abuse. These include identifying sites within the CNS that show an induction 
of the IE response as a result of acute drug administration as well as sites that 
exhibit a response upon withdrawal. Since Fos mapping does not necessarily 
equate with activity mapping as determined by 2-deoxyglucose, this may be 
important in directing attention to regions of the nervous system that were 
previously unsuspected of playing any role in drug responses and dependence. 
The use of conventional neuropharmacological reagents in these systems can 
resolve some aspects of the synaptology of the IE response to drugs. Thus, it 
may provide a means to understand some of the signaling molecules and 
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