Figure 7.

Increased extinction responding and cue-induced reinstatement in female Npas2 mutant mice during the dark phase. Following progressive ratio, responding on the cocaine-associated lever was extinguished over the course of at least 10 d. Following extinction, responding on the active lever was reinstated with the presence of previously cocaine-associated cues. We found a very slight increase in extinction responding during the light phase in (A) female and (B) male mutant mice, as indicated by a (C) trending effect of genotype. On the other hand, during the dark phase, extinction responding was only increased in (D) female Npas2 mutants, while (E) male mutants were unaffected. F, This sex difference was confirmed by an interaction between session, sex, and mutation. A similar pattern was detected for cue-induced reinstatement, wherein (G–I) no effects were found during the light phase, but (J) female and (K) male mice were differentially affected by Npas2 mutation in the dark phase. L, A trending interaction was found and female Npas2 mutants responded significantly more during cue-induced reinstatement, suggesting increased drug seeking, but no differences were observed in males. Mean + SEM; individual data points are shown in G–L, #p < 0.1, *p < 0.05, **p < 0.01, n = 4–11.