Figure 2. Ago2 controls the motivation to self-administer cocaine in mice. (A) Ago2 controls cocaine intake in mice. Cocaine self-administration was measured for Drd2-Cre; Ago2fl/fl (n = 12) and Ago2fl/fl control littermates (n = 10). Graph represents the number of cocaine infusions (0.3 mg/kg/infusion) earned under a FR5TO20 s schedule of reinforcement over 10 consecutive days. (B) Ago2 deficiency in Drd2-expressing MSNs results in a downward shift in the cocaine D–R curve. The unit dose of cocaine available for self-administration was varied according to a within-subjects Latin square design (0.3 mg/kg/infusion), and the effects of responding to each dose of cocaine were assessed in Drd2-Cre; Ago2fl/fl mice (n = 12) and Ago2fl/fl controls (n = 10). Data are presented as number of cocaine infusions earned on the last day of access to each dose of cocaine. (C) Loss of Ago2 in Drd2 neurons abolishes conditional place preference to cocaine. Drd2-Cre; Ago2fl/fl (n = 11) and Ago2fl/fl control (n = 5) mice were tested for their preference for an environment associated with cocaine versus saline injections and the percentage of time (%) spent in the saline or cocaine-paired side is shown. (D) Ago2 does not control food reward. The response for food reward was assessed in Drd2-Cre; Ago2fl/fl (n = 12) and Ago2fl/fl (n = 10) littermate controls. Mice responded for food under a FR5TO20 s schedule of reinforcement. No differences in operant performance were detected between genotypes. (E and F) Ago2 does not control acute cocaine-induced locomotor activity (E) or cocaine-induced anxiety (F). Open field analysis was used to measure locomotor activity and thigmotaxis in Drd2-Cre; Ago2fl/fl and Ago2fl/fl control mice (n = 8/genotype) at basal level (10 min), followed by 100 µl i.p. saline injection (for 10 min), followed by acute cocaine injection (20 mg/kg i.p., 60 min). The bar graphs represent the total distance moved (in centimeters; E) and the ratio of total distance moved in the center versus total arena (F). Statistical analysis was performed using a two-way ANOVA (A–D) and a repeated measure two-way ANOVA (E and F). Data are shown as means; error bars represent ± SEM. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
Figure 2.

Ago2 controls the motivation to self-administer cocaine in mice. (A) Ago2 controls cocaine intake in mice. Cocaine self-administration was measured for Drd2-Cre; Ago2fl/fl (n = 12) and Ago2fl/fl control littermates (n = 10). Graph represents the number of cocaine infusions (0.3 mg/kg/infusion) earned under a FR5TO20 s schedule of reinforcement over 10 consecutive days. (B) Ago2 deficiency in Drd2-expressing MSNs results in a downward shift in the cocaine D–R curve. The unit dose of cocaine available for self-administration was varied according to a within-subjects Latin square design (0.3 mg/kg/infusion), and the effects of responding to each dose of cocaine were assessed in Drd2-Cre; Ago2fl/fl mice (n = 12) and Ago2fl/fl controls (n = 10). Data are presented as number of cocaine infusions earned on the last day of access to each dose of cocaine. (C) Loss of Ago2 in Drd2 neurons abolishes conditional place preference to cocaine. Drd2-Cre; Ago2fl/fl (n = 11) and Ago2fl/fl control (n = 5) mice were tested for their preference for an environment associated with cocaine versus saline injections and the percentage of time (%) spent in the saline or cocaine-paired side is shown. (D) Ago2 does not control food reward. The response for food reward was assessed in Drd2-Cre; Ago2fl/fl (n = 12) and Ago2fl/fl (n = 10) littermate controls. Mice responded for food under a FR5TO20 s schedule of reinforcement. No differences in operant performance were detected between genotypes. (E and F) Ago2 does not control acute cocaine-induced locomotor activity (E) or cocaine-induced anxiety (F). Open field analysis was used to measure locomotor activity and thigmotaxis in Drd2-Cre; Ago2fl/fl and Ago2fl/fl control mice (n = 8/genotype) at basal level (10 min), followed by 100 µl i.p. saline injection (for 10 min), followed by acute cocaine injection (20 mg/kg i.p., 60 min). The bar graphs represent the total distance moved (in centimeters; E) and the ratio of total distance moved in the center versus total arena (F). Statistical analysis was performed using a two-way ANOVA (A–D) and a repeated measure two-way ANOVA (E and F). Data are shown as means; error bars represent ± SEM. *, P < 0.05; **, P < 0.01; ***, P < 0.001.

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