PMC:400732 / 8147-11657 JSONTXT

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No genotype differences were found in the ability to dig through unscented sand for a hidden food pellet (F1,128 = 1.26, p \u003e 0.27).\n\nWild-type mice outperform D2R-/- mice in an odor-driven, stimulus-discrimination, operant task\nTo master the odor-driven stimulus discrimination task, D2R-/- mice required significantly more trials (Fig. 3A: t(14) = 2.20; p \u003c 0.05) and committed more errors (Fig. 3B: t(14) = 2.92; p \u003c 0.05) than D2R+/+ mice to learn to associate a specific odor with the presence or absence of the food reinforcer. However, both genotypes did learn the task and eventually maintained accurate discrimination for a minimum of 8 correct responses out of 10 trials.\n\nMice lacking dopamine D2 receptors engage in unreinforced behavior in a perseverative manner following reversal of reinforcement contingencies\nD2R-/- mice repeatedly failed to inhibit previously established learning contingencies during reversal trials (Fig. 4A: t(14) = 3.54; p \u003c 0.01) and committed significantly more reversal errors than D2R+/+ mice (Fig. 4B: t(14)= 3.18; p \u003c 0.01). Categorical division of reversal errors (Ferry et al., 2000) – digging in the dish that did not contain the food pellet (S-) (error of commission; Fig. 5A) versus failing to respond within 3-min of presentation (error of omission; Fig. 5B) revealed that both genotypes chiefly committed errors of commission versus errors of omission (D2R-/- mice, U = 0.00; p \u003c 0.01; D2R+/+ mice U = 9.00, p \u003c 0.05), D2R-/- mice committed more commission errors than D2R+/+ mice (U = 5.00, p \u003c 0.05), and there were no differences between D2R-/- and D2R+/+ mice in omission errors (U = 27.5, p = 0.65). Moreover, the number of commission errors committed during the first reversal session (an index of stimulus bound perseveration, where all animals are responding to the reversed contingencies for the first time; Fig. 6) indicated a deficit in the D2R-/- mice compared to the D2R+/+ mice (U = 8.5, p \u003c 0.01). Finally, in an attempt to assess whether perseveration occurred across multiple reversal sessions (Fig. 7), we analyzed the number of commission errors emitted before relearning the reinforcement contingencies during the reversal sessions. The data depicted were collected from subjects that had not achieved the 80% performance criterion. Therefore, the number of D2R+/+ mice represented in session #1 is 8, in session #2 n = 8, session #3 n = 6 (2 mice met our criterion), in session # 4 n = 5 (three met the criterion). Following session 5, the remaining 5 D2R+/+ mice had met criteria. For the D2R-/- mice, each point on the graph represents 8 subjects. None of the D2R-/- mice achieved the criterion of 80% accuracy by session 5. For the overall 2-way ANOVA, there was a significant difference between genotypes for the number of perseverative errors (F1,51 = 16.61, p \u003c 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