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D. BRUNNER, E. LUDVIG, R. ABNER, X. ZHUANG, P. POON, F. BALCI

We examined interval timing in mice that underexpress the dopamine transporter (DAT) and thus have chronically higher levels of extracellular dopamine. Dopamine has been proposed as a neural substrate for an internal clock, with higher dopamine levels increasing the speed of the clock and producing earlier timed responding. A group of 8 of DAT KD mice were tested with a dual peak procedure, an interval-timing task. Mice were reinforced for pressing one of two levers after a fixed amount of time (30 or 45 s) had elapsed from lever extension. Only 1 lever was available at a time, and each lever was associated with a single duration. Occasional probe (peak) trials were interspersed where the lever remained extended, but no reward was available. On these peak trials, the DAT KD mice indeed began responding earlier in the interval than corresponding wild-type (WT) mice, but showed a peak in responding and gave up around the same time as the WT mice. This pattern of results greatly resembles the effects of increased reward magnitude on responding in the peak procedure. Administration of raclopride (0.2, 0.6, and 1.2 mg/kg), a D2 antagonist, obliterated most of the differences between DAT KD and WT mice, suggesting that the effects of chronically elevated dopamine levels on interval timing were mediated by the D2 receptor sub-type. An additional cohort of DAT KD mice was trained on a visual attention task, and no deficits were observed, confirming that the changes in timed behavior were not attentionally mediated. These data are challenging for existing theories of the role of dopamine in interval timing, but are perhaps better explained by supposing that tonic dopamine levels code for average reward rate, as suggested in recent reinforcement learning models.