FIGURE 6. GBR- 12909 increases Fos immunoreactivity in the olfactory 
tubercle and islands of Calleja. Generally, control sections (see 
figure 4) are nearly blank except for the occasional darkly stained 
neuronal nucleus in the olfactory tubercle and adjacent pyriform 
cortex. After cocaine, large numbers of nuclei are densely 
stained in both the tubercle and the islands. (64X magnification; 
antibody dilution, 1:10, 000) 
mRNA were seen as rapidly as 10 minutes and continued to accumulate at 20 
and 60 minutes to reach a level (fivefold to eightfold increase) comparable to 
that obtained with the 30 mg/kg IP dose of cocaine (not shown). In general, our 
molecular observations of GBR-12909 were similar to those of cocaine. 
The rapidity and selective regional distribution of the mRNA increase and 
subsequent increase in protein content suggest that treatment with a 
dopamine reuptake blocker rapidly induces c -fos gene expression. To test 
the involvement of dopamine receptors in mediating the effect of cocaine, 
we pretreated the rats with several doses of either the D1 selective antagonist 
SCH-23390 or the D2 antagonist sulpiride. Using immunocytochemistry and 
counts of Fos-immunoreactive cell nuclei, we observed that SCH-23390 
pretreatment at a dose of 10 jig/kg partially attenuated the effect of 30 mg/kg 
of cocaine, and a dose of 50 pig/kg completely blocked the effect of cocaine 
(figures 8 and 9). Pretreatment with sulpiride partially attenuated the effect of 
191 
