Summary: A new study reveals how social rank influences addiction vulnerability by altering dopamine pathways in the brain. Low-ranking male mice showed stronger reward signals and weaker control circuits, making them more prone to seek methamphetamine, while high-ranking mice had better balance and resistance.
Enhancing the mesocortical “control” pathway through optogenetics reduced drug-seeking and improved social rank, suggesting experience-based changes can reshape addiction risk. Interestingly, these effects were sex-specific, with female mice showing drug-seeking behavior regardless of status.
Key Facts:
- Circuit Imbalance: Low social rank is linked to stronger reward signals and weaker executive control.
- Experience Matters: Winning experiences elevated social rank and reduced drug-seeking in males.
- Sex-Specific Findings: Female addiction behavior was not influenced by social rank.
Source: Chinese Academy of Science
Drug addiction poses a global public health challenge, with limited therapeutic options and modest efficacy. While numerous studies have shown that social status profoundly impacts mental health and addiction susceptibility, its neural mechanisms remain unclear.
Now, however, a research team led by Prof. ZHU Yingjie from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences has revealed the neural mechanisms by which social rank influences vulnerability to drug addiction.
The study was published in Nature Neuroscience on May 12.
Using a suite of cutting-edge neuroscience tools such as fiber photometry, fast-scan cyclic voltammetry, optogenetic manipulation, and volumetric imaging, the researchers explored both functional and structural differences in the dopamine systems of male rodents occupying different social ranks.
These tools allowed them to measure real-time neuronal activity, detect rapid chemical changes (particularly dopamine), manipulate neural circuits with light, and capture high-speed 3D images of brain activity.
The findings revealed that an animal’s social rank influences its tendency to seek methamphetamine (METH) by affecting the mesolimbic and mesocortical pathways—two key dopamine pathways in the brain.
The mesolimbic pathway delivers dopamine to the nucleus accumbens (NAc) and promotes reward-seeking behavior, whereas the mesocortical pathway, which projects to the medial prefrontal cortex (mPFC) and supports executive control, helping suppress compulsive drug use.
“Low-ranking mice exhibit a stronger ‘reward’ circuit and a weaker ‘control’ circuit —like a high-powered car with faulty brakes—making them more likely to seek drugs. In contrast, high-ranking mice have a more balanced system, with effective ‘brakes’ that help them resist addiction,” explained Prof. ZHU.
To understand these mechanisms, the researchers used both pharmacological and optogenetic approaches to manipulate dopamine signaling.
When dopamine-related proteins in the NAc of low-ranking male mice were reduced, their METH-seeking behavior declined. In contrast, when dopamine fibers in the mPFC of high-ranking male mice were damaged, drug-seeking behavior increased.
Most strikingly, activating the mesocortical dopamine pathway via optogenetic stimulation not only made the mice win a social competition test more often; it also made them much less likely to seek METH in subsequent trials.
Notably, the study also found that these effects were sex-specific: Female mice exhibited METH-seeking behavior regardless of social rank, suggesting different neurobiological underpinning of addiction risk in male and females.
Importantly, the researchers found that introducing winning experiences to low-ranking male mice not only elevated their social rank but also reduced later drug-seeking behavior. These behavioral changes were linked to functional and structural remodeling in both the mesocortical and mesolimbic dopamine pathways.
This study introduces a novel neurobiological framework linking social status, dopamine circuit dynamics, and addiction vulnerability.
“By boosting an individual’s sense of social achievement or simulating successful experiences, it may be possible—at the neural level—to ‘strengthen the brakes and ease off the accelerator,’ thereby reducing addiction risk,” said Prof. ZHU.
He noted that the study also supports the development of non-invasive stimulation therapies aimed at reducing addiction vulnerability.
About this dopamine and addiction research news
Author: LU Qun
Source: Chinese Academy of Science
Contact: LU Qun – Chinese Academy of Science
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Social rank modulates methamphetamine-seeking in dominant and subordinate male rodents via distinct dopaminergic pathways” by ZHU Yingjie et al. Nature Neuroscience
Abstract
Social rank modulates methamphetamine-seeking in dominant and subordinate male rodents via distinct dopaminergic pathways
Social status has a profound impact on mental health and propensity towards drug addiction. However, the neural mechanisms underlying the effects of social rank on drug-seeking behavior remain unclear.
Here we found that dominant male rodents (based on the tube test) had denser mesocortical dopaminergic projections and were more resistant to methamphetamine (METH)-seeking, whereas subordinates had heightened dopaminergic function in the mesolimbic pathway and were more vulnerable to METH seeking.
Optogenetic activation of the mesocortical dopaminergic pathway promoted winning and suppressed METH seeking in subordinates, whereas lesions of the mesocortical pathway increased METH seeking in dominants.
Elevation of social rank with forced win training in subordinates led to remodeling of the dopaminergic system and prevented METH-seeking behavior.
In females, however, both ranks were susceptible to METH seeking, with mesocorticolimbic pathways comparable to those in subordinate males.
These results provide a framework for understanding the neural basis of the impact of social status on drug-seeking.
