Expression levels of most neurotransmitter-specific genes declined during late adolescence to early adulthood (P38-P88), with AE binge treatment enhancing this developmental downregulation. Interestingly, AE treatment altered the developmental trajectories of different genes in different patterns, suggesting unique responses of each gene (Fig. 3(r), Fig. 4). Dopamine receptor 4 (D4DR) mRNA was decreased about 71% on P38 following adolescent binge treatment (Fig. 3, Table 1, *p<0.05, t-test of normalized ΔCt values). Interestingly, D4DR underwent a 70% developmental decline between P38 and P88, whereas binge ethanol treated animals showed no additional developmental reduction, i.e. expression on P38 and P88 following binge ethanol treatment were both 70% below P38 control levels (Table 1, Fig. 3). Since dopamine circuitry continues to develop during adolescence in frontal cortex we used immunohistochemistry (IHC) to assess D4DR expression. The orbitofrontal cortex (OFC) of adolescent rats showed strong punctate D4DR+IR that was 44% less in the OFC of P38 binge ethanol treated mice compared to P38 adolescent control mice (Figure 3, *p<0.05). Since the developmental decrease in D4DR mRNA mimicked the AE induced decrease and no developmental change
