Cocaine-Induced lEGs: P28 
5 
Cortex Striatum 
| c -fos 
E3 C -jun 
□ z/f/268 
FIGURE 3. Graph depicting the striatal and cortical induction (vs. saline) of c- 
fos, c-jun, and zif/268 mRNA in 28-day-old rat pups. Cocaine , 40 
mg/kg/I P, was injected 45 minutes prior to sacrifice. C-fos 
elevation in cortex (2-fold) and striatum (4.6-fold) was greater 
than that of c-jun or zif/268. 
The specificity of cocaine-induced increases in AP-1 DNA binding activity 
is demonstrated by competition with unlabeled double-stranded DNA 
oligonucleotide containing the AP-1 sequence (figure 5, lanes 5 and 6; 
figure 6, lanes 3 and 7), but absence of competition is demonstrated by 
an oligonucleotide containing the AP-2 sequence (figure 6, lane 4). 
CONCLUSIONS 
The authors have demonstrated cocaine-induced changes in gene expression 
during rat brain development at two levels of analysis: (1) regional and 
temporal specificity of mRNA induction for the lEGs c -fos, c-jun , and zif/268 
from northern gel experiments and (2) functional confirmation that in striatum 
AP-1 DNA binding activity is increased in parallel with the elevation in IEG 
mRNA described above. These experiments provide evidence that mRNA 
changes occur within 45 minutes, and AP-1 DNA binding changes occur 
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