Figure 6.

The reinforcing and motivational properties of cocaine were increased in Npas2 mutant mice. During a dose-response analysis (0–1 mg/kg/infusion) at ZT2 (light phase), Npas2 mutant mice self-administered more infusions of cocaine across dose in both (A) female and (B) male Npas2 mutant mice. C, This significant increase in cocaine intake across sex suggests an increase in the reinforcing properties of cocaine. At ZT4, the reinforcing properties of cocaine were also increased in (D) female and (E) male mutant mice. Here, effects appear to be greater in female mutants, but (F) no sex effect was found. During progressive ratio testing, (G) female and (H) male Npas2 mutant mice again worked harder for each infusion of cocaine. I, Although a significant increase in breakpoint ratio was found across sex, this effect seems to be driven primarily by female mutant mice. Similar results are found during the dark phase, wherein break point ratio was increased in (J) female and (K) male Npas2 mutants. L, Again, female mutants appear to be particularly affected, but no significant effect of sex was found. Mean + SEM; individual data points are shown in G–L, *p < 0.05, **p < 0.01, ***p < 0.001, n = 4–11.