Decreased motivational value in an instrumental task after a single injection of haloperidol with quantitative assessment of dopamine D2-like receptor occupancy

The motivation to engage in action is regulated by valuation of predicted outcome comprised from external factor (i.e., incentive) and internal factor (i.e., drive). Function-mediated dopamine D2-like receptor (D2R) is widely known to be involved in processing motivation, incentive, and drive. However, it is unclear how the transmission via D2R is related to the computation of motivational value from these factors. To address this issue, we quantitatively assessed the relationship between motivational value of instrumental action and dopamine D2-like receptor availability after systemic injection of D2R antagonist. We performed positron emission tomography (PET) measurements for D2R binding with [11C]raclopride in 2 monkeys. With a systemic injection of a low dose of D2R antagonist, haloperidol (0.01mg/kg, i.m.), occupancy of D2R in the striatum was 74~81%. This occupancy lasted to at least post-injection day 3 (~40% occupancy), and [11C]raclopride binding recovered to the pre-treatment level at day 7. We tested 2 monkeys with reward-size task (Minamimoto et al., 2009), in which they were required to release a bar to receive predicted water rewards (1, 2, 4 or 8 drops). The error rate of the task (i.e., proportion of trials with low motivation) increased during days 0 to 3 after the haloperidol injection. We quantified the motivational value by using error rate (E), since it is inversely related to the predicted reward size (R): E = 1/aR, where a is a free parameter. The best-fit parameter a was discounted from the pre-treatment level by 50% at day 0 and by 30~40% at day 3, returning to the pre-treatment level at day 7, suggesting that the impact of outcome on motivational value attenuated in parallel with D2R occupancy. In contrast, the injection of haloperidol did not affect sucrose preference or water amount intake in the home cage, indicating that incentive valence and drive were unimpaired. These results suggest that attenuation of dopamine transmission via D2 receptors reduces computation of motivational value from external and internal information.Neuroscience 2012, SfN\u27s 42th annual meetin