Hyperdopaminergia in rats is associated with reverse effort-cost dependent performance

Background: Dopamine is implicated in the effort-based control of motivational processes; however, whether tonic dopamine regulates the effort-cost impact on motivation, is still debated.Aims: The rats lacking the dopamine transporter (DAT), which have dramatically increased levels of the synaptic dopamine, were used in the present study to elucidate the role of the synaptic dopamine in motivational processes.Methods: To study the reward-related processes, the progressive ratio 3 (PR3) operant schedule of food reinforcement (the ratio increases by 3 after each earned reinforcer) was performed in adult male rats (DAT knockouts (DAT-KO), heterozygotes (DAT-HT) and wild-types (DAT-WT)).Results: During the PR3 session, the response rate of DAT-KO rats was gradually increased following the augmented required number of responses. In contrast, the local response rate of DAT-WT and DAT-HT decreased. d-Amphetamine sulfate salt (3 mg/kg, i.p.) altered the local response rate dynamics in DAT-WT, which became similar to that of DAT-KO. Interestingly, the reduction in response rate at low effort demands was associated with decreased rate of entries into the magazine tray in DAT-WT rats treated with amphetamine (3 mg/kg) but not in DAT-KO rats.Conclusions: Our results suggest that the elevated tonic synaptic dopamine can strongly affect motivation/effort-cost relation in rodents.