{"title":"Higher levels of D2R and D3R in the frontal-striatal regions are associated with reduced perseverative reward seeking after opioid abstinence.","authors":"Yingying Li, Xigeng Zheng, Cong Gao, Shao Li, Zhengkui Liu, Meixuan Lv, Fei Xiao, Yunjing Bai","doi":"10.3389/fnbeh.2025.1552055","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The lower levels of dopamine D2 receptor (D2R) in the striatum and the heightened levels of dopamine D2 receptor (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.</p><p><strong>Methods: </strong>This study utilized two high-cost tasks to investigate perseverative reward seeking, specifically conflict-based approaching behavior and persistent responding behavior under a progesterone receptor (PR) procedure. Additionally, D2R and D3R levels in the medial prefrontal cortex (mPFC) and striatum were examined through Western blotting.</p><p><strong>Results: </strong>After each task, male rats were divided into two subpopulations: high-approaching vs. low-approaching and high-responding vs. low-responding. Rats treated with morphine (MOR) exhibited a 3 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.</p><p><strong>Discussion: </strong>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 control their reward-seeking behavior better.</p>","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":"19 ","pages":"1552055"},"PeriodicalIF":2.6000,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171296/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Behavioral Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fnbeh.2025.1552055","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: The lower levels of dopamine D2 receptor (D2R) in the striatum and the heightened levels of dopamine D2 receptor (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.
Methods: This study utilized two high-cost tasks to investigate perseverative reward seeking, specifically conflict-based approaching behavior and persistent responding behavior under a progesterone receptor (PR) procedure. Additionally, D2R and D3R levels in the medial prefrontal cortex (mPFC) and striatum were examined through Western blotting.
Results: After each task, male rats were divided into two subpopulations: high-approaching vs. low-approaching and high-responding vs. low-responding. Rats treated with morphine (MOR) exhibited a 3 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.
Discussion: 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 control their reward-seeking behavior better.
期刊介绍：
Frontiers in Behavioral Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the neural mechanisms underlying behavior. Field Chief Editor Nuno Sousa at the Instituto de Pesquisa em Ciências da Vida e da Saúde (ICVS) is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
This journal publishes major insights into the neural mechanisms of animal and human behavior, and welcomes articles studying the interplay between behavior and its neurobiological basis at all levels: from molecular biology and genetics, to morphological, biochemical, neurochemical, electrophysiological, neuroendocrine, pharmacological, and neuroimaging studies.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
