VTA dopamine inputs activate accumbal D1 receptors to promote alcohol seeking

  • iScience. 2026 Jun 2;29(6):116198. doi: 10.1016/j.isci.2026.116198.
Junwei Xiong  1  2 ,  Mengyao Dou  1 ,  Xinxin Li  1  2 ,  Ting Zeng  2  3 ,  Yongliang Liu  3 ,  Huizhen Dai  1 ,  Chenyu Du  1 ,  Xiaowei Shi  1 ,  Xiangmin Xu  1 ,  Xiaofei Wang  1 ,  Xiaofeng Zhu  1 ,  Jianing Wei  1 ,  Dandan Cui  1 ,  Yanzhong Guan  1  2
Affiliations
  • 1. Department of Physiology & Neurobiology, Mudanjiang Medical University, Mudanjiang 157011, China.
  • 2. Heilongjiang Province Key Laboratory of Mechanism and Prevention of Substance Dependence Disease, Mudanjiang 157011, China.
  • 3. Development Anesthesiology, Mudanjiang Medical University, Mudanjiang 157011, China.
PMID: 42291205 DOI: 10.1016/j.isci.2026.116198
Abstract

The mesolimbic dopamine system is central to cue-induced alcohol craving, but the role of D1 receptors (D1R) in the nucleus accumbens (NAc) remains unclear. Here, we show that cue-induced, but not context-elicited, alcohol seeking selectively upregulates NAc D1R protein expression in mice, which positively correlates with craving intensity. Systemic D1R antagonist SCH23390 suppresses cue-induced seeking and reverses c-Fos activation in the NAc and ventral pallidum. Chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons attenuates craving, an effect fully rescued by intra-NAc D1R agonist SKF38393 without affecting locomotion. These findings establish that dopaminergic projections from the VTA to the NAc drive cue-specific alcohol seeking through D1 receptor-dependent manner.

Keywords
Paleobiology; Paleogenetics; Phylogenetics; Zoology.