Cocaine B/AP-1 
Cocaine A/AP-1 
Cocaine B 
Cocaine A 
Saline B 
Saline A 
FIGURE 5. Gel retardation assay performed on striatal extracts (20 ng) from 
P28 rats prepared from two sets (A and B) of three animals 
injected IP with saline (lanes 1 and 2) or cocaine 30 mg/kg (lanes 
3, 4, 5, and 6) 2 hours before sacrifice. The arrow designates the 
position of the specific band induced by cocaine administration. 
Cocaine induces a 2- to 2. 5- fold increase in specific AP-1 binding 
activity (compare lane 1 vs. lane 2, and lane 3 vs. lane 4). The 
specific band is competed by cold AP-1 oligonucleotide at 100- 
fold excess over labeled probe (lanes 5 and 6). 
temporal specificity of altered IEG expression by cocaine for nervous system 
development are profound. Normal brain development requires complex and 
finely tuned genetic coordination, where individual neurons undergo phenotypic 
differentiation to assume unique chemical, physiologic, and connectional 
features. The maturation of synaptic circuitry, chemical neurotransmission, 
and neurophysiologic repertoires that subserve the normal acquisition of 
developmental skills requires a complex orchestration of genetic regulation 
and environmental influences. Drug-induced alterations during such critical 
periods may irrevocably alter CNS form and function. The experiments 
outlined characterize some of the phenomenology of IEG activation by drugs 
of abuse in developing rat brain. The significance of this work relates to the 
hypothesis that (1) as transcription factors, lEGs may play a critical role in 
the genetic events that shape human behavior and (2) drug-induced IEG 
dysregulation may have long-lasting structural and functional consequences 
when perturbed during brain development. 
168 
