ORIGINAL RESEARCH article
Front. Behav. Neurosci.
Sec. Motivation and Reward
Volume 19 - 2025 | doi: 10.3389/fnbeh.2025.1552055
Higher levels of D2R and D3R in the frontal-striatal regions are associated with reduced perseverative reward seeking after opioid abstinence Authors
Provisionally accepted
- 1Other
- 2Institute of Psychology, Chinese Academy of Sciences (CAS), Beijing, Beijing Municipality, China
- 3Department of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases,, Dalian Medical University, Dalian, Liaoning, China
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The lower levels of D2R in the striatum and the heightened levels of D3R in the midbrain have been linked to impulsive behavior and risky decision-making associated with drug dependence.While D3R has been considered a potential target for treating drug dependence, the connection between D3R in the prefrontal-striatal regions and maladaptive drug-related behaviors remains poorly understood. This study utilized two high-cost tasks to investigate perseverative reward seeking, specifically conflict-based approaching behavior and persistent responding behavior under a PR procedure. Additionally, D2R and D3R levels in the mPFC and striatum were examined through western blotting. Male rats were divided into two subpopulations, high-approaching versus low-approaching, or high-responding versus low-responding, following each task. Rats treated with morphine exhibited a three-fold increase in the likelihood of developing high-approaching or high-responding behaviors compared to drug-naïve rats. D2R expression was higher in the ventral striatum of morphine-treated, low-approaching rats than high-approaching rats, negatively correlating with approaching behaviors within the morphine-exposed group. After six consecutive PR sessions, D3R levels in the dorsal striatum differed significantly between morphine-treated, low-responding rats and morphine-treated, high-responding rats, negatively correlating with responding behaviors within the morphine-exposed group. An intriguing finding was the non-linear relationships, resembling an inverted U shape, observed between the level of D3R in the mPFC and reward-seeking behaviors, as revealed by both tasks. The elevated or relatively higher levels of D2R and D3R in the frontal-striatal regions may serve as protective factors for individuals abstaining from opioids, enabling them to better control their reward-seeking behavior.
Keywords: Morphine, reward seeking, perseveration, D2/D3, Striatum, Prefrontal Cortex
Received: 27 Dec 2024; Accepted: 12 May 2025.
Copyright: © 2025 Li, Zheng, Gao, Li, Liu, Lv, Xiao and Bai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yunjing Bai, Institute of Psychology, Chinese Academy of Sciences (CAS), Beijing, 100101, Beijing Municipality, China
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