Cocaine-Induced lEGs: Adult 
8 
CD 
C 
■ M 
Cortex Striatum 
B c -fos 
E3 G-yi/n 
□ z/7/268 
FIGURE 4. Graph depicting induction (vs. saline) by cocaine (40 mg/kg/IP 
injected 45 minutes prior to sacrifice) of c-fos , c-jun, and zif/268 
in adult cortex and striatum. The most significant response is the 
induction of c-fos mRNA (6.6-fold) in striatum. 
within 2 hours after exposing developing brain to cocaine. One central 
question concerns the identification of target genes that, by virtue of having 
AP-1 (or AP-1-like) DNA binding sequences in their regulatory regions, 
may be altered in their expression. Candidates include synthetic enzymes 
for neurotransmitters (e.g., tyrosine hydroxylase), peptide neurotransmitter 
precursors (e.g., substance P), and growth factors (e.g., nerve growth factor) 
among many other genes. The regional and temporal specificity of I EG 
induction by cocaine identifies a mechanism by which selective alteration 
of target gene expression can be altered during development consequent 
to drug exposure. 
Significance 
Exposure of the developing brain to cocaine altered the expression of three 
IEG transcription factors, which as third messengers may influence the 
expression of cascades of genes. The implications of the regional and 
167 
