PMC:4017736 / 5357-6799 JSONTXT

{"project":"2_test","denotations":[{"id":"24193139-2899326-113748126","span":{"begin":201,"end":203},"obj":"2899326"},{"id":"24193139-12445717-113748127","span":{"begin":473,"end":475},"obj":"12445717"},{"id":"24193139-122445-113748128","span":{"begin":477,"end":479},"obj":"122445"},{"id":"24193139-18347339-113748129","span":{"begin":1063,"end":1065},"obj":"18347339"}],"text":"MPH increases MPH potency and MPH-induced dopamine overflow\nThe reinforcing and rewarding effects of many drugs of abuse are related to their ability to elevate dopamine in the nucleus accumbens (NAc) 20. While the NAc shell is involved in the acute rewarding effects of drugs and acquisition of self-administration, the NAc core plays a critical role in cue-reward learning as well as continued responding for drugs after repeated administration as in the current paradigm21, 22. We found dopamine uptake in the NAc core to be supersensitive to MPH inhibition following MPH self-administration (two-way ANOVA; F (1, 9) = 25.11, p \u003c 0.05; Fig 1 D, E) (n = 5 control, 6 MPH self-administration), which is consistent with our microdialysis data demonstrating increased MPH-induced dopamine overflow in the NAc (two-way ANOVA; F (1, 5) = 20.80, p \u003c 0.001; Supplementary Fig S1A) (n = 4 control, 5 MPH self-administration) The proposed mechanism for augmented MPH potency is increased DAT levels, which has been suggested to modulate the potency of dopamine releasers23. Indeed, after MPH self-administration (n = 31 per group), the maximal rate of dopamine uptake was increased (Vmax; Student’s t-test; t60 = 2.434, p \u003c 0.01) (Fig 1 G, H) as was the peak amplitude of stimulated dopamine release (Fig 1 H; Student’s t-test; t24 = 2.719, p \u003c 0.01). We showed previously that the increase in Vmax after MPH was due to increased total DAT levels24."}