Some studies have highlighted the crucial role of aversion in addiction treatment. The pathway from the anterior paraventricular thalamus (PVT) to the shell of the nucleus accumbens (NAc) has been reported as an essential regulatory pathway for processing aversion and is also closely associated with substance addiction. However, its impact on alcohol addiction has been relatively underexplored. Therefore, this study focused on the role of the PVT-NAc pathway in the formation and relapse of alcohol addiction-like behaviour, offering a new perspective on the mechanisms of alcohol addiction. The chemogenetic inhibition of the PVT-NAc pathway in male mice resulted in a notable decrease in the establishment of ethanol-induced conditioned place aversion (CPA), and NAc-projecting PVT neurons were recruited due to aversive effects. Conversely, activation of the PVT-NAc pathway considerably impeded the formation of ethanol-induced conditioned place preference (CPP). Furthermore, during the memory reconsolidation phase, activation of this pathway effectively disrupted the animals' preference for alcohol-associated contexts. Whether it was administered urgently 24 h later or after a long-term withdrawal of 10 days, a low dose of alcohol could still not induce the reinstatement of ethanol-induced CPP. Our results demonstrated PVT-NAc circuit processing aversion, which may be one of the neurobiological mechanisms underlying aversive counterconditioning, and highlighted potential targets for inhibiting the development of alcohol addiction-like behaviour and relapse after long-term withdrawal.

中文翻译：

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室旁丘脑至伏隔核回路激活可减少雄性小鼠酗酒行为的长期复发

一些研究强调了厌恶在成瘾治疗中的关键作用。据报道，从前室旁丘脑（PVT）到伏隔核壳（NAc）的通路是处理厌恶的重要调节通路，也与物质成瘾密切相关。然而，它对酒精成瘾的影响尚未得到充分研究。因此，本研究重点探讨PVT-NAc通路在酒精成瘾样行为形成和复发中的作用，为酒精成瘾机制提供新的视角。雄性小鼠中 PVT-NAc 通路的化学遗传学抑制导致乙醇诱导的条件性位置厌恶 (CPA) 的建立显着减少，并且由于厌恶效应而招募了 NAc 投射的 PVT 神经元。相反，PVT-NAc 途径的激活极大地阻碍了乙醇诱导的条件性位置偏好（CPP）的形成。此外，在记忆重新巩固阶段，该通路的激活有效地破坏了动物对与酒精相关的环境的偏好。无论是24小时后紧急给药还是长期停药10天后，低剂量酒精仍不能诱导乙醇诱导的CPP恢复。我们的结果证明了 PVT-NAc 回路处理厌恶，这可能是厌恶性反调节的神经生物学机制之一，并强调了抑制酒精成瘾样行为的发展和长期戒断后复发的潜在目标。