Operant Costs Modulate Dopamine Release to Self-Administered Cocaine.

The costs associated with obtaining illicit drugs can fluctuate depending upon the relative drug availability. As a consequence of the changing costs, the effort that one must exert to obtain drugs is dynamic. Considerable evidence illustrates a critical role for dopamine in the ventral medial striatum in mediating drug reinforcement. However, little is known regarding how dopamine release is affected by changes in the costs associated with earning drugs. We used fast-scan cyclic voltammetry to determine how changes in the operant requirement affected dopamine release to self-administered cocaine in male rats. Dopamine release to cocaine infusions increased across trials during self-administration sessions using a fixed-ratio reinforcement schedule with a low operant requirement. However, increasing the operant requirement abolished the within-session elevation in dopamine release to drug rewards. This effect was not due to underlying changes in preinfusion dopamine levels and was not explained by cocaine levels in the brain. This within-session increase in dopamine release to cocaine infusions reemerged when the operant requirement was lowered. Under a progressive ratio reinforcement schedule, there was no increase in dopamine release to drug rewards across trials, which contrasts with prior studies demonstrating an increase in dopamine release to food rewards. Collectively, these findings illustrate that the influence of operant costs on reward-evoked dopamine release depends upon type of reward that can be earned (e.g., food or drug).