| First Author | Sun X | Year | 2023 |
| Journal | Neuropharmacology | Volume | 222 |
| Pages | 109273 | PubMed ID | 36252615 |
| Mgi Jnum | J:344487 | Mgi Id | MGI:7386554 |
| Doi | 10.1016/j.neuropharm.2022.109273 | Citation | Sun X, et al. (2023) Accumbal adenosine A(2A) receptor inactivation biases for large and costly rewards in the effort- but not delay-based decision making. Neuropharmacology 222:109273 |
| abstractText | The cost-benefit decision-making (CBDM) is critical to normal human activity and a diminished willingness to expend effort to obtain rewards is a prevalent/noted characteristic of neuropsychiatric disorders such as schizophrenia, Parkinson's disease. Numerous studies have identified nucleus accumbens (NAc) as an important locus for CBDM control but their neuromodulatory and behavioral mechanisms remain largely under-explored. Adenosine A(2A) receptors (A(2A)Rs), which are highly concentrated in the striatopallidal neurons, can integrate glutamate and dopamine signals for controlling effort-related choice behaviors. While the involvement of A(2A)Rs in effort-based decision making is well documented, the role of other decision variables (reward discrimination) in effort-based decision making and the role of A(2A)R in delay-based decision making are less clear. In this study, we have developed a well-controlled CBDM behavioral paradigm to manipulate effort/cost and reward independently or in combination, allowing a dissection of four behavioral elements: effort-based CBDM (E-CBDM), delay-based CBDM (D-CBDM), reward discrimination (RD), effort discrimination (ED), and determined the effect of genetic knockdown (KD) of NAc A(2A)R on the four behavioral elements. We found that A(2A)R KD in NAc increased the choice for larger, more costly reward in the E-CBDM, but not D-CBDM. Furthermore, this high-effort/high-reward bias was attributable to the increased willingness to engage in effort but not the effect of discrimination of reward magnitude. Our findings substantiate an important role of the NAc A(2A)R in control of E-CBDM and support that pharmacologically targeting NAc A(2A)Rs would be a useful strategy for treating the aberrant effort-based decision making in neuropsychiatric disorders. |
