从杏仁核基底外侧核到伏隔核壳的兴奋性传递通过 AMPA 受体调节异丙酚的自我给药,Addiction Biology

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从杏仁核基底外侧核到伏隔核壳的兴奋性传递通过 AMPA 受体调节异丙酚的自我给药
Addiction Biology ( IF 3.1 ) Pub Date : 2023-07-06 , DOI: 10.1111/adb.13310
Zhanglei Dong _{1,

2,

3} , Saiqiong Xiang _{1,

2,

3} , Chi Pan _{1,

2,

3} , Chenchen Jiang ₄ , Suhao Bao _{1,

2,

3} , Wangning Shangguan _{1,

2,

3} , Ruifeng Zeng _{1,

2,

3} , Jun Li _{1,

2,

3} , Qingquan Lian _{1,

2,

3} , Binbin Wu _{1,

2,

3}

Affiliation

异丙酚的成瘾特性已在人类和大鼠身上得到证实。从杏仁核基底外侧核 (BLA) 到伏隔核 (NAc) 的谷氨酸能传递调节寻求奖励的行为；特别是，NAc shell (NAsh) 与奖励寻求反应有关。先前的研究表明，AMPA 受体（AMPAR）和多巴胺 D1 受体（D1R）在 NAc 介导的药物成瘾中存在相互作用，但 BLA 至 NAsh 和 AMPAR 的回路是否调节异丙酚成瘾仍不清楚。我们训练成年雄性 Sprague-Dawley 大鼠进行异丙酚自我给药，以检查 NAsh 中动作电位（AP）和自发兴奋性突触后电流（sEPSC）的变化。此后，使用 BLA 中腺相关病毒载体显微注射的光遗传学刺激来探索 BLA-to-NAsh 对异丙酚自我给药行为（1.7 mg/kg/注射）的影响。检测 NAsh 中 NBQX（0.25–1.0 μg/0.3 μl/位点）或媒介物预处理对异丙酚自我给药行为的影响、NAc 中 AMPARs 亚基的表达和 D1R/ERK/CREB 信号通路。结果显示，自用异丙酚的大鼠中，APs的数量、sEPSCs的幅度和频率均有所增加。异丙酚自行给药在NpHR3.0-EYFP组中受到抑制，但在ChR2-EYFP组中则有促进作用，但NBQX预处理可减弱这种作用。NBQX预处理还显着降低NAc中GluA2亚基和D1R的表达，但没有改变GluA1和ERK/CREB信号通路的表达。证据支持 BLA-to-NAsh 回路在调节异丙酚自我给药中发挥重要作用，并表明这种中央奖励处理可能通过 NAsh 中 AMPAR 和 D1R 之间的相互作用发挥作用。

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The excitatory transmission from basolateral nuclues of amygdala to nucleus accumbens shell regulates propofol self-administration through AMPA receptors

Propofol addictive properties have been demonstrated in humans and rats. The glutamatergic transmission from basolateral nucleus of amygdala (BLA) to the nucleus accumbens (NAc) modulates reward-seeking behaviour; especially, NAc shell (NAsh) is implicated in reward-seeking response. Previous studies indicated the interactions between AMPA receptors (AMPARs) and dopamine D1 receptor (D1R) in NAc mediated drug addiction, but whether the circuit of BLA-to-NAsh and AMPARs regulate propofol addiction remains unclear. We trained adult male Sprague–Dawley rats for propofol self-administration to examine the changes of action potentials (APs) and spontaneous excitatory postsynaptic currents (sEPSCs) in the NAsh. Thereafter, optogenetic stimulation with adeno-associated viral vectors microinjections in BLA was used to explore the effect of BLA-to-NAsh on propofol self-administration behaviour (1.7 mg/kg/injection). The pretreatment effects with NBQX (0.25–1.0 μg/0.3 μl/site) or vehicle in the NAsh on propofol self-administration behaviour, the expressions of AMPARs subunits and D1R/ERK/CREB signalling pathway in the NAc were detected. The results showed that the number of APs, amplitude and frequency of sEPSCs were enhanced in propofol self-administrated rats. Propofol self-administration was inhibited in the NpHR3.0-EYFP group, but in the ChR2-EYFP group, there was a promoting effect, which could be weakened by NBQX pretreatment. NBQX pretreatment also significantly decreased the expressions of GluA2 subunit and D1R in the NAc but did not change the expressions of GluA1 and ERK/CREB signalling pathway. The evidence supports a vital role of BLA-to-NAsh circuit in regulating propofol self-administration and suggests this central reward processing may function through the interaction between AMPARs and D1R in the NAsh.

更新日期：2023-07-07

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