Another IEG that has been extensively studied in the two MSN subtypes is FosB. Acute exposure to cocaine induces FosB in D1+ MSNs (Berretta et al., 1992), whereas chronic exposure induces ΔFosB, a stable product of the FosB gene generated by alternative splicing (Hope et al., 1994; Nestler et al., 2001; Nestler, 2008), in D1+ MSNs (Nye et al., 1995; Moratalla et al., 1996; Lee et al., 2006). Similar findings are observed with many other drugs of abuse as well as with natural rewards such as food, sex, and wheel running. For example, chronic wheel running, which is a natural reward (Iversen, 1993; Belke, 1997; Lett et al., 2000), induces ΔFosB in D1+ MSNs but not D2+ MSNs (Werme et al., 2002). To gain functional insight into the role of ΔFosB in the two MSNs, our group generated NSE-tTa lines, termed 11A and 11B, which direct transgene expression to either D1+ or D2+ MSNs, respectively (Chen et al., 1998; Kelz et al., 1999; Werme et al., 2002). Line 11A mice crossed with a Tet-Op ΔFosB line show increased responses to
