Alterations in effort-related decision-making induced by stimulation of dopamine D1, D2, D3, and corticotropin-releasing factor receptors in nucleus accumbens subregions

Rationale Nucleus accumbens (NAc) dopamine (DA) plays an integral role in overcoming effort costs, as blockade of D-1 and D-2 receptors reduces the choice of larger, more-costly rewards. Similarly, the stress neuropeptide corticotropin-releasing factor (CRF) modulates DA transmission and mediates stress-induced alterations in effort-related choice. Objectives The current study explored how excessive stimulation of different DA receptors within the NAc core and shell alters effort-related decision-making and compared these effects to those induced by CRF stimulation. Methods Male Long Evans rats were well-trained on an effort-discounting task wherein they choose between a low-effort/low-reward and a high-effort/high-reward lever where the effort requirement increased over blocks (2-20 presses). Dopamine D-1 (SKF 81297, 0.2-2 mu g), D-2/3 (quinpirole, 1-10 mu g), or D-3 (PD 128,907, 1.5-3 mu g) receptor agonists, or CRF (0.5 mu g), were infused into the NAc core or shell prior to testing. Results Stimulation of D-2/3 receptors with quinpirole in the NAc core or shell markedly reduced the choice of high-effort option and increase choice latencies, without altering preference for larger vs smaller rewards. Stimulation of D-1 or D-3 receptors did not alter choice, although SKF 81297 infusions into the shell reduced response vigor. In comparison, core infusions of CRF flattened the discounting curve, reducing effortful choice when costs were low and increasing it when costs were high. Conclusions Excessive stimulation of NAc D-2 receptors has detrimental effects on effort-related decision-making. Furthermore, CRF stimulation induces dissociable effects on decision-making compared with those induced the effects of stimulation of different DA receptors.