Figure 4.

D32^fl/fl/D2cre⁺ mice exhibit sustained glucose-derived reinforcement learning and impaired learning flexibility. (a) Design of conditioned flavor preference experiment (PT, pretest; CD1, conditioning day 1; CD2, conditioning day 2; RV1, reversal conditioning day 1; RV2, reversal conditional day 2). (b) D32^fl/fl/D2cre⁺ mice and controls (D32^fl/fl/D2cre^-) did not differ in intake of grape- or cherry-flavored fructose solutions before conditioning (PT session). During conditioning (CD1 and CD2), D32^fl/fl/D2cre⁺ mice consumed significantly more (c) grape-paired glucose but not (d) cherry-paired fructose vs controls. ***P⩽0.001, two-sample t-test. Both groups consumed more grape-paired glucose over cherry-paired fructose. (e) After conditioning (TD1), D32^fl/fl/D2cre⁺ and control mice consumed significantly more grape-flavored fructose compared with cherry-flavored fructose. ***P⩽0.001, paired t-test. D32^fl/fl/D2cre⁺ mice consumed significantly more grape-flavored fructose vs controls, whereas the two groups did not differ in cherry-paired fructose intake. **P⩽0.01, two-sample t-test. During reversal conditioning, D32^fl/fl/D2cre⁺ and controls did not differ in (f) grape-paired fructose or (g) cherry-paired glucose intake. Both groups readily consumed more cherry-paired glucose compared with grape-paired fructose solutions. (h) After reversal conditioning, controls readily consumed more cherry-paired fructose over grape-paired fructose but D32^fl/fl/D2cre⁺ mice did not. *P⩽0.05, paired t-test. Data are shown as mean±SEM.