PMID- 36252615 OWN - NLM STAT- MEDLINE DCOM- 20221122 LR - 20221224 IS - 1873-7064 (Electronic) IS - 0028-3908 (Linking) VI - 222 DP - 2023 Jan 1 TI - Accumbal adenosine A(2A) receptor inactivation biases for large and costly rewards in the effort- but not delay-based decision making. PG - 109273 LID - S0028-3908(22)00332-X [pii] LID - 10.1016/j.neuropharm.2022.109273 [doi] AB - 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. CI - Copyright (c) 2022. Published by Elsevier Ltd. FAU - Sun, Xiaoting AU - Sun X AD - Molecular Neuropharmacology Laboratory and Eye-Brain Research Center, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology & Optometry and Vision Science, Wenzhou Medical University, Wenzhou, 325027, China. FAU - Liu, Min AU - Liu M AD - Molecular Neuropharmacology Laboratory and Eye-Brain Research Center, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology & Optometry and Vision Science, Wenzhou Medical University, Wenzhou, 325027, China. FAU - Xu, Xinyu AU - Xu X AD - Molecular Neuropharmacology Laboratory and Eye-Brain Research Center, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology & Optometry and Vision Science, Wenzhou Medical University, Wenzhou, 325027, China. FAU - Shi, Chennan AU - Shi C AD - Molecular Neuropharmacology Laboratory and Eye-Brain Research Center, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology & Optometry and Vision Science, Wenzhou Medical University, Wenzhou, 325027, China. FAU - Zhang, Liping AU - Zhang L AD - Molecular Neuropharmacology Laboratory and Eye-Brain Research Center, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology & Optometry and Vision Science, Wenzhou Medical University, Wenzhou, 325027, China. FAU - Yao, Zhimo AU - Yao Z AD - Molecular Neuropharmacology Laboratory and Eye-Brain Research Center, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology & Optometry and Vision Science, Wenzhou Medical University, Wenzhou, 325027, China. FAU - Chen, Jiangfan AU - Chen J AD - Molecular Neuropharmacology Laboratory and Eye-Brain Research Center, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology & Optometry and Vision Science, Wenzhou Medical University, Wenzhou, 325027, China. Electronic address: chenjf555@gmail.com. FAU - Wang, Qin AU - Wang Q AD - Molecular Neuropharmacology Laboratory and Eye-Brain Research Center, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; State Key Laboratory of Ophthalmology & Optometry and Vision Science, Wenzhou Medical University, Wenzhou, 325027, China. Electronic address: msqwang@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221014 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Receptor, Adenosine A2A) RN - K72T3FS567 (Adenosine) SB - IM MH - Humans MH - *Receptor, Adenosine A2A MH - *Adenosine/pharmacology MH - Decision Making/physiology MH - Reward MH - Bias OTO - NOTNLM OT - Adenosine A(2A) Receptors OT - Delay-based cost-benefit decision making OT - Effort-based cost-benefit decision making OT - Motivation OT - Nucleus accumbens COIS- Declaration of competing interest The authors declare that they have no competing interests. EDAT- 2022/10/18 06:00 MHDA- 2022/11/23 06:00 CRDT- 2022/10/17 19:22 PHST- 2022/07/07 00:00 [received] PHST- 2022/09/22 00:00 [revised] PHST- 2022/09/24 00:00 [accepted] PHST- 2022/10/18 06:00 [pubmed] PHST- 2022/11/23 06:00 [medline] PHST- 2022/10/17 19:22 [entrez] AID - S0028-3908(22)00332-X [pii] AID - 10.1016/j.neuropharm.2022.109273 [doi] PST - ppublish SO - Neuropharmacology. 2023 Jan 1;222:109273. doi: 10.1016/j.neuropharm.2022.109273. Epub 2022 Oct 14.