Activation of lEGs by Cocaine 
The constraints on drug-induced IEG repertoire imposed by cell phenotype 
in adult rats were addressed by Young and colleagues (1991) and Graybiel 
and colleagues (1990), who reported that cocaine-stimulated fos induction in 
striatum could be completely blocked by pretreatment with a D1 antagonist 
(SCH 23390). Interpretation of experiments employing the D2 antagonist 
(sulpiride) was complex because D2 antagonists independently activate c-fos 
expression. Coupled with the knowledge that in striatum different (though 
not mutually exclusive) populations of neurons have D1 vs. D2 receptors 
(Gerfen et al. 1990), one can conclude that receptor phenotype of striatal 
neurons is one of the cellular determinants conferring cocaine inducibility 
of IEG expression. This idea is supported by anatomic studies (Berretta et 
al. 1991) that have identified the subset of neurons in adult rat striatum that 
express c-Fos after cocaine administration as containing DARP-32, a marker 
for neurons expressing D1 receptors. By analogy, the susceptibility of the 
developing brain to be affected by cocaine may relate to the maturation of 
presynaptic (e.g., aminergic projections), postsynaptic (e.g., D1 receptors), 
and/or intrinsic (e.g., cellular signal transduction pathways) features specific 
for a given cell type in a given brain region at a particular point in development. 
EXPERIMENTAL RESULTS 
The authors have performed northern gel analyses to characterize the acute 
induction of the lEGs c -fos, c -jun, and zii ! 268 in three areas of rat brain: 
dorsolateral neocortex, striatum, and cerebellum. Rats were examined at 
four different ages: postnatal (P) day 8 (P8, roughly equivalent to term 
for a human fetus), 2 weeks of age (PI 5), 4 weeks of age (P28), and at 
maturity. Animals were injected with cocaine (40 mg/kg in .9 percent saline) 
and sacrificed 45 minutes later, when regional brain dissections were 
performed on ice. Total cellular RNA was prepared by a modification of 
the method from Berger and Chirgwin (1989). Samples were homogenized 
in 4M guanidinium isothiocyanate followed by centrifugation through a 5.7M 
cesium chloride pad. RNA was quantitated, and 30-jo.g samples were run on 
a formaldehyde gel. RNA was transferred to a nylon membrane, cross-linked, 
and hybridized with nick-translated probes for c -fos, c -jun, or ziU 268 and for 
cyclophilin (unregulated internal reference gene). Autoradiograms were 
quantitated with densitometry and represented graphically. Figure 1 (P8), 
figure 2 (PI 5), figure 3 (P28), and figure 4 (adult) depict severalfold induction 
(vs. saline-injected controls) of lEGs by region, representing an average from 
two experiments for each plot (three to four animals pooled for each condition, 
for each experiment). There is considerable specificity evident with regard to 
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