Pan Chi, Mao Xinyu, Jiang Yujie, Jiang Chenchen, Qiu Jiani, Zhang Yantong, Chen Gang, Xu Mengting, Li Jun, Wu Binbin
Department of Anesthesiology, Perioperative and Pain Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Addict Biol. 2025 Aug;30(8):e70078. doi: 10.1111/adb.70078.
Propofol is recognized as an addictive substance in both humans and animals. Increasing evidence suggests that the prelimbic cortex (PL) within the medial prefrontal cortex (mPFC), plays an important role in mediating drug addiction. In this study, we trained adult male Sprague-Dawley rats to establish a model of locomotor sensitization (LS). Moreover, optogenetic inhibition of glutamatergic neurons within the PL inhibited the LS of propofol, whereas optogenetic activation of glutamatergic neurons within the PL promoted the LS of propofol. This effect could be blocked by NBQX (a competitive AMPAR antagonist) pretreatment. Subsequently, a microinjection of NBQX (0.25-1 μg/0.3 μL/site) or saline was administered into the bilateral PL to further examine the impact of AMPARs on the LS of propofol. We found that NBQX pretreatment significantly inhibited both the distance and activity in sensitized rats. The expressions of GluA1 and GluA2 subunits of AMPARs, phosphorylated NR1 subunit of NMDARs, D1Rs, phosphorylated ERK and phosphorylated CREB within mPFC were statistically significantly decreased after NBQX pretreatment, whereas, the expressions of total ERK, total CREB and total NR1 subunit remained unchanged. This evidence verifies the instrumental role of AMPARs within the PL in mediating the LS of propofol, and the NMDAR-D1R/ERK/CREB signalling pathway may act as a potential mechanism.
丙泊酚在人类和动物中均被视为成瘾性物质。越来越多的证据表明，内侧前额叶皮质（mPFC）内的前边缘皮质（PL）在介导药物成瘾中起重要作用。在本研究中，我们训练成年雄性Sprague-Dawley大鼠建立运动敏化（LS）模型。此外，对PL内谷氨酸能神经元进行光遗传学抑制可抑制丙泊酚诱导的LS，而对PL内谷氨酸能神经元进行光遗传学激活则可促进丙泊酚诱导的LS。这种效应可被NBQX（一种竞争性AMPA受体拮抗剂）预处理阻断。随后，向双侧PL微量注射NBQX（0.25 - 1μg/0.3μL/位点）或生理盐水，以进一步研究AMPA受体对丙泊酚诱导的LS的影响。我们发现，NBQX预处理显著抑制了敏化大鼠的运动距离和活动。NBQX预处理后，mPFC内AMPA受体的GluA1和GluA2亚基、NMDA受体的磷酸化NR1亚基、D1受体、磷酸化ERK和磷酸化CREB的表达在统计学上显著降低，而总ERK、总CREB和总NR1亚基的表达保持不变。这一证据证实了PL内AMPA受体在介导丙泊酚诱导的LS中的重要作用，并且NMDAR-D1R/ERK/CREB信号通路可能是其潜在机制。
