Involvement of dopamine D3 receptor in impulsive choice decision-making in male rats.

Study authors Hui Shen and Zilu Ma

Featured Paper of the Month – October 2024

Published in Neuropharmacology by Hui Shen, Zilu Ma and Yihong Yang, et al. of the NIDA IRP Magnetic Resonance Imaging and Spectroscopy Section.

Summary

Impulsive decision-making, such as opting for a smaller, immediate reward over a larger, delayed one, is associated with addiction and impulse control disorders. However, the neural mechanisms underlying impulsive behavior remain unclear. In this study, we used the delay-discounting task (DDT) to identify rats with different levels of impulsivity. Our results revealed that highly impulsive rats exhibited lower levels of D2 receptors, and more prominently, D3 receptors in the nucleus accumbens (NAc), but not in other brain regions. To explore the role of the D3 receptor further, we administered drugs that specifically target this receptor. FOB02-04, a novel compound that activates the D3 receptor, reduced impulsive behavior, while VK4-116, a drug that blocks the D3 receptor, increased impulsivity in both high- and low-impulsive rats. These findings suggest that impulsive decision-making is linked to reduced D3 receptor expression in the NAc and that selective D3 receptor agonists could hold potential for reducing impulsivity in individuals prone to impulsive behavior.

Publication Information

Shen, Hui; Ma, Zilu; Hans, Emma; Duan, Ying; Bi, Guo-Hua; Chae, Yurim C; Bonifazi, Alessandro; Battiti, Francisco O; Newman, Amy Hauck; Xi, Zheng-Xiong; Yang, Yihong

Involvement of dopamine D3 receptor in impulsive choice decision-making in male rats Journal Article

In: Neuropharmacology, vol. 257, pp. 110051, 2024, ISSN: 1873-7064.

Abstract | Links

@article{pmid38917939,

title = {Involvement of dopamine D3 receptor in impulsive choice decision-making in male rats},

author = {Hui Shen and Zilu Ma and Emma Hans and Ying Duan and Guo-Hua Bi and Yurim C Chae and Alessandro Bonifazi and Francisco O Battiti and Amy Hauck Newman and Zheng-Xiong Xi and Yihong Yang},

url = {https://pubmed.ncbi.nlm.nih.gov/38917939/},

doi = {10.1016/j.neuropharm.2024.110051},

issn = {1873-7064},

year  = {2024},

date = {2024-10-01},

urldate = {2024-10-01},

journal = {Neuropharmacology},

volume = {257},

pages = {110051},

abstract = {Impulsive decision-making has been linked to impulse control disorders and substance use disorders. However, the neural mechanisms underlying impulsive choice are not fully understood. While previous PET imaging and autoradiography studies have shown involvement of dopamine and D2/3 receptors in impulsive behavior, the roles of distinct D1, D2, and D3 receptors in impulsive decision-making remain unclear. In this study, we used a food reward delay-discounting task (DDT) to identify low- and high-impulsive rats, in which low-impulsive rats exhibited preference for large delayed reward over small immediate rewards, while high-impulsive rats showed the opposite preference. We then examined D1, D2, and D3 receptor gene expression using RNAscope in situ hybridization assays. We found that high-impulsive male rats exhibited lower levels of D2 and D3, and particularly D3, receptor expression in the nucleus accumbens (NAc), with no significant changes in the insular, prelimbic, and infralimbic cortices. Based on these findings, we further explored the role of the D3 receptor in impulsive decision-making. Systemic administration of a selective D3 receptor agonist (FOB02-04) significantly reduced impulsive choices in high-impulsive rats but had no effects in low-impulsive rats. Conversely, a selective D3 receptor antagonist (VK4-116) produced increased both impulsive and omission choices in both groups of rats. These findings suggest that impulsive decision-making is associated with a reduction in D3 receptor expression in the NAc. Selective D3 receptor agonists, but not antagonists, may hold therapeutic potentials for mitigating impulsivity in high-impulsive subjects.},

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pubstate = {published},

tppubtype = {article}

}