LY 171555, it is inferred that inhibition of D2-dopamine receptors either in 
striatum or in neurons that project to it elicit fos induction, perhaps by a 
disinhibition of striatal neurons. 
Although both amphetamine and cocaine induced fos in striatum, they did so 
with different anatomical distributions (Graybiel et al. 1990). Furthermore, there 
were pharmacological distinctions in the mechanisms linking the two agents to 
fos expression, suggesting that they acted via the same transmitter system but 
in different cell populations. For example, in the caudatoputamen, acute and 
chronic reserpine pretreatment suppressed subsequent c -fos induction by 
cocaine but not amphetamine, suggesting that the two drugs utilize different 
stores of monoamines (Graybiel et al. 1990). 
Fos-lacZ Transgenic Mice 
To advance the use of fos mapping, a line of transgenic mice were bred that 
carry a fos-lacZ transgene (Smeyne and colleagues 1992). There were several 
reasons for doing this. First, the technique would be less time consuming 
and costly than immunohistochemistry and in situ hybridization. Second, it 
would avoid the ambiguity of cross-reaction of antisera with Fos-related 
proteins. Third, it would serve to define the regulatory elements required for c- 
fos expression in vivo. Fourth, it would provide the first step in devising an 
inducible gene system for use in mice. Fifth, by mutational analysis of the fos 
promoter in the context of a fusion gene, it may be possible to derive insights 
into the second messengers and transcription factors critical in specific neurons 
following a particular challenge. 
A fusion gene was constructed that comprised bacterial lacZ ((3-galactosidase) 
fused in-frame into exon 4 of c -fos that was tested by stable transfection into 
B104 neuroblastoma cells (Schilling et al. 1991). The gene contained all the 
known 5'-upstream regulatory sequences of c -fos as well as all introns and 
exons (which also contain intragenic regulatory sequences) and several 
kilobases of 3' flanking genomic DNA. Thus, the fusion gene also includes the 
polyadenylation consensus sequence from c-/bs and the Shaw-Kamen element 
believed to confer the rapid degradation of c -fos mRNA (Schilling et al. 1991). 
Furthermore, since the fusion is in the fourth exon of c -fos, the fusion protein 
retains the leucine-zipper motif and other sequences that direct the protein to 
the nucleus. It was expected that inducible nuclear (3-galactosidase activity 
would be observed from the construct. This was deemed important since it 
would greatly improve the sensitivity and resolution of the technique when 
applied in animo. In a stably transfected B104 neuroblastoma cell line, 
inducible nuclear |3-galactosidase activity could be demonstrated following 
treatment with serum, phorbol ester, and dibutyryl cyclic AMP, as well as 
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