Dramatically Decreased Cocaine Self-Administration in Dopamine But Not Serotonin Transporter Knock-Out Mice

Cocaine self-administration and food-maintained behavior in wild-type, SERT^−/−, and DAT^−/− mice. a, Under an FR 1 schedule of reinforcement, most DAT^−/− mice failed to self-administer cocaine, while SERT mutation had no effect. Group sizes: wild-type, N = 13; DAT ^−/−, N = 5; SERT^−/−, N = 11, DAT^−/−SERT^−/−, N = 7. b, A minority of DAT^−/− mice that responded under the FR 1 schedule stopped self-administering when the response requirement was increased, while wild-type and SERT^−/− mice maintained their cocaine intake. Group sizes: wild-type, N = 11; DAT ^−/−, N = 3; SERT^−/−, N = 12. c, Wild-type mice and SERT^−/− mice, but not DAT^−/− mice, self-administered cocaine under a PR schedule of reinforcement. Group sizes: wild-type, N = 8; DAT ^−/−, N = 3; SERT^−/−, N = 10. d, Food maintained comparable responding in all three genotypes under the PR schedule. Group sizes: wild-type, N = 10; DAT ^−/−, N = 4; SERT^−/−, N = 14. † < 0.05, †† < 0.01, ††† < 0.001 versus wild-type; independent samples t test. *p < 0.05, **p < 0.01, ***p < 0.001, versus saline (S) (a, c), versus FR 1 (b), or versus water (W) (d); paired-sample t test. Data are group means ± SEM.