The objective of the present study was to use a sensitive liquid chromatography (LC)-MS procedure (Higgs et al., 2005) to determine the effects of repeated ethanol administration on protein expression in the ACB shell of P and NP rats. The ACB shell was selected because this region of the ACB is involved in mediating reinforcement, whereas the core portion does not appear to be involved in reinforcement processes (Ikemoto et al., 1997). The repeated ethanol injection procedure was used because this protocol has been shown to produce differential effects on monoamine neurotransmission in the ACB of P, NP and W rats (Smith and Weiss, 1999). In addition, the present experimental approach permitted changes in protein levels to be detected in a key limbic region of rats that exhibit disparate alcohol drinking characteristics. In the present study, it was important to include W rats for comparison purposes to help interpret differences between P and NP rats as being mainly due to unique responses to ethanol in the P line, or unique responses to ethanol in the NP line. The hypothesis to