Restoration of prosocial behavior in rats after heroin self-administration via chemogenetic activation of the anterior insular cortex.
Restoration of prosocial behavior in rats after heroin self-administration via chemogenetic activation of the anterior insular cortex.
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通过前岛叶皮质的化学遗传学激活，海洛因自我给药后大鼠的亲社会行为恢复。
DOI：
10.1080/17470919.2020.1746394
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发表时间：
2020
影响因子：
2
通讯作者：
Olive,MFoster
中科院分区：
文献类型：
--
作者：
Tomek,SevenE;Stegmann,GabrielaM;Leyrer-Jackson,JonnaM;Piña,Jose;Olive,MFoster
前岛叶皮层（AIC）介导成瘾的各种社会，情感和内感受性成分。最近，我们证明了在大鼠中海洛因自我给药后亲社会行为的破坏，通过检查动物在同时获得海洛因的同时从塑料限制器中拯救其cagraphy的倾向来评估。为了研究海洛因诱导的亲社会功能缺陷是由AIC介导的可能性，本研究探讨了化学激活或抑制兴奋性AIC锥体神经元对海洛因诱导的亲社会功能缺陷的影响。在建立基线拯救行为后，大鼠接受编码对照病毒（AAV-CaMKIIα-GFP）、刺激性DREADD（AAV-CaMKIIα-hM 3Dq-mCherry）（实验1）或抑制性DREADD（AAV-CaMKIIα-hM 4Di-mCherry）（实验2）的病毒载体双侧输注到AIC中。然后允许大鼠自我给予海洛因（0.06 mg/kg/输注）6小时/天，持续2周。在重新评估亲社会行为之前，向动物施用氯氮平-N-氧化物（1.5mg/kg，i. p.）以评估AIC的化学发生激活或抑制的作用。相对于对照组动物，AIC的化学发生激活逆转了海洛因诱导的救援行为的缺陷，而AIC的化学发生抑制则没有效果。我们推测，AIC的刺激性神经调节可能是恢复阿片类药物滥用中亲社会性的一种新方法。
The anterior insular cortex (AIC) mediates various social, emotional, and interoceptive components of addiction. We recently demonstrated a disruption of prosocial behavior following heroin self-administration in rats, as assessed by examining the animals’ propensity to rescue its cagemate from a plastic restrainer while having simultaneous access to heroin. To examine the possibility that heroin-induced deficits in prosocial function are mediated by the AIC, the present study examined the effects of chemogenetic activation or inhibition of excitatory AIC pyramidal neurons on heroin-induced prosocial deficits. After establishment of baseline rescuing behavior, rats received bilateral infusions of viral vectors encoding either a control virus (AAV-CaMKIIα-GFP), stimulatory DREADD (AAV-CaMKIIα-hM3Dq-mCherry) (Experiment 1), or inhibitory DREADD (AAV-CaMKIIα-hM4Di-mCherry) (Experiment 2), into the AIC. Rats were then allowed to self-administer heroin (0.06 mg/kg/infusion) 6 hr/day for 2 weeks. Prior to re-assessment of prosocial behavior, animals were administered clozapine-N-oxide (1.5 mg/kg, i.p.) to assess the effects of chemogenetic activation or inhibition of the AIC. Relative to control animals, chemogenetic activation of the AIC reversed deficits in rescuing behavior induced by heroin, whereas chemogenetic inhibition of the AIC had no effect. We hypothesize that stimulatory neuromodulation of the AIC may be a novel approach for restoring prosociality in opiate abuse.