Inhaled N,N-Dimethyltryptamine Diminishes Connectivity between the Ventral Tegmental Area and the Nucleus Accumbens : relevance to pathologies of mesolimbic and mesocortical pathways
OpenAlex – September 17, 2025
Source: OpenAlex
Summary
Reduced connectivity in the midbrain-nucleus accumbens pathway, often heightened in addiction, was observed after inhaling N,N-dimethyltryptamine (DMT) among 11 experienced participants. Notably, connectivity increased between the nucleus accumbens and anterior cingulate cortex, as well as between the medial prefrontal cortex and anterior cingulate cortex. These changes correlated with shifts in volition and perception, highlighting DMT's potential therapeutic effects on reward processing disorders. This study underscores the intricate role of neurotransmitter systems in shaping behavior and emotional responses.
Abstract
Abstract Reward processing is a broad psychological construct that can be parsed into distinct components known as “reinforcement learning” (learning), “reward responsiveness” (liking), and “motivation to obtain a reward” (wanting). Dysfunctions in reward processing in mesolimbic and mesocortical pathways, are a core feature of many pathologies. Psychedelics have been proposed as a treatment option for multiple disorders affecting the reward system, but mechanistic studies are lacking.In the present study, we evaluated the effects of inhaled N,N-dimethyltryptamine (DMT) with a particular focus on the connectivity of the mesocorticolimbic circuitry. Our within-subject pharmacoimaging design included 11 healthy participants with prior experience in psychedelics. In the active condition, DMT was self-administered immediately before MRI acquisition, while in the control condition there was no administration.We found decreased connectivity between the right nucleus accumbens (NAc) and the left ventral tegmental area (VTA), increased connectivity between the right NAc and anterior cingulate cortex (ACC) and increased connectivity between the medial prefrontal cortex (mPFC) and the ACC. These results correlated with changes in volition and perception, as measured with the hallucination rating scale.In sum, we found reduced connectivity in the midbrain-NAc pathway, which connectivity is often increased in addiction, and increased connectivity between reward/affective regions and the ACC. These findings suggest a potential therapeutic potential of psychedelics in disorders affecting reward processing.