Regulation effect of orbitofrontal cortex-dorsomedial striatum neural circuits on addiction motivation in susceptible mice
10.3867/j.issn.1000-3002.2025.08325
- VernacularTitle:眶额叶皮质-背内侧纹状体神经环路对成瘾易感小鼠成瘾动机的调控作用
- Author:
Huimin ZHU
1
;
Xingfang CUN
;
Ning WU
;
Jin LI
;
Rui SONG
Author Information
1. 南京中医药大学,江苏 南京 210023;军事医学研究院神经精神药理学北京市重点实验室,北京 100850;国家安全特需药品全国重点实验室,北京 100039
- Publication Type:Journal Article
- Keywords:
drug addiction;
drug motivation;
heroin;
orbitofrontal cortex;
dorsomedial striatum
- From:
Chinese Journal of Pharmacology and Toxicology
2025;39(8):561-568
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To study the neural circuits involved in regulating the strong drug-taking motivation in susceptible mice,and provide novel insights into the intervention and treatment of drug addiction.METHODS A heroin intermittent-access(Int A)self-administration model was established.Mice were divided into susceptible,unsusceptible,and non-learnt subgroups based on parameters,such as the number of times of drug infusions,effective lever presses,and breakpoints(BP)in the progres-sive ratio schedule during the drug acquisition phase.Using chemogenetic techniques,the neural projection from the orbitofrontal cortex(OFC)to the dorsomedial striatum(DMS)was selectively manipulated in the progressive ratio schedule,and its impact on drug motivation was assessed across the three subgroups.RESUITS Selectively inhibiting the OFC-DMS circuit significantly reduced the BP in susceptible mice,with no significant effect on the other two subgroups.Conversely,selective activation of this pathway significantly increased BP in susceptible mice,but had no impact on the other subgroups.CONCLU-SION The OFC-DMS circuit specifically modulates drug motivation behavior in susceptible mice,but not in the unsusceptible,and non-learnt subgroups.
