@article{APS11536,
author = {Xing-fang Cun and Man-yi Jing and Meng-die Yang and Ning Wu and Jin Li and Rui Song},
title = {A novel superior colliculus circuit mediates visual cue-driven methamphetamine taking and seeking},
journal = {Acta Pharmacologica Sinica},
volume = {47},
number = {6},
year = {2026},
keywords = {},
abstract = {Addictive substances transform environmental cues into potent conditioned cues through reward-based associative learning. While visual cues are known to amplify drug-seeking behavior and trigger relapse, the neural circuits mediating their motivational salience remain incompletely understood. Here, we identified the superior colliculus (SC) as a critical encoder of drug-related visual information via gating reinstatement through a defined SC–VTA–NAcore pathway. We established a methamphetamine (MA) self-administration model in mice with fiber photometry, optogenetic, and chemogenetic techniques. Using fiber photometry, we discovered that the monosynaptic SC–VTA pathway exhibited selective activation during exposure to drug-paired visual cues, which demonstrated a stable cue encoding. Optogenetic inhibition of SC–VTA projections completely abolished cue-induced reinstatement, while activation potentiated reinstatement. Transsynaptic tracing confirmed a SCGlu+–VTADA+–NAcore circuit. Bidirectional manipulation of this pathway demonstrated its necessity and sufficiency for controlling cue-triggered reinstatement. Our results establish the SC as a sensory-motivational hub that transforms visual drug cues into relapse-promoting signals through a hardwired midbrain circuit. The discovery of this SC–VTA–NAcore pathway provides both a mechanistic framework for understanding cue-driven addiction and concrete targets for interventions.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/11536}
}