Abstract
Drug-associated environmental cues can trigger drug-seeking behavior and precipitate relapse. In this study, we determined that the claustrum (CL) connects the ventral tegmental area (VTA) with the medial prefrontal cortex (mPFC), forming the VTA–CL–mPFC circuit. Using a methamphetamine (METH) conditioned place preference (CPP) model in male mice, we found that manipulating the VTA–CL–mPFC circuit or CL neuronal ensemble receiving projections from VTA and projecting to mPFC (VTA–CL–mPFC) could disrupt the retrieval of METH-paired context memory, resulting in the blockage of the acquisition of METH CPP in male mice. During the process, dopamine release and dopamine 1-like receptor–mediated activation of CL neurons were required for the retrieval of METH-induced reward memory in male mice. These findings reveal a midbrain–cortical circuit orchestrated by CL neurons that plays an essential role in the retrieval of drug-paired environmental cue memory.
Authors
Ziheng Zhao, Yuhong He, Yang Liu, Quying Feng, Hee Young Kim, Yu Fan, Xiaowei Guan
Figure 6
The DA release and D1R levels on CLGlu neurons increase during the retrieval of METH-induced reward memory.
Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)