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.

前岛叶皮层 (AIC) 介导成瘾的各种社交、情绪和内感受成分。我们最近证明了在大鼠中自我给药海洛因后亲社会行为的破坏，这是通过检查动物在同时获得海洛因的同时从塑料固定器中拯救其笼子的倾向来评估的。为了检查海洛因诱导的亲社会功能缺陷由 AIC 介导的可能性，本研究检查了化学遗传激活或兴奋性 AIC 锥体神经元对海洛因诱导的亲社会缺陷的影响。建立基线拯救行为后，大鼠接受双侧输注病毒载体，编码对照病毒 (AAV-CaMKIIα-GFP)、刺激性 DREADD (AAV-CaMKIIα-hM3Dq-mCherry)（实验 1）、或抑制性 DREADD (AAV-CaMKIIα-hM4Di-mCherry)（实验 2），进入 AIC。然后允许大鼠自我给药海洛因（0.06 毫克/千克/输注）6 小时/天，持续 2 周。在重新评估亲社会行为之前，给动物注射氯氮平-N-氧化物（1.5 毫克/公斤，腹腔注射）以评估化学遗传激活或 AIC 抑制的影响。相对于对照动物，AIC 的化学遗传激活逆转了海洛因诱导的拯救行为的缺陷，而 AIC 的化学遗传抑制没有效果。我们假设 AIC 的刺激性神经调节可能是一种在阿片类药物滥用中恢复亲社会性的新方法。给动物施用氯氮平-N-氧化物（1.5 毫克/千克，腹腔注射）以评估化学遗传激活或 AIC 抑制的影响。相对于对照动物，AIC 的化学遗传激活逆转了海洛因诱导的拯救行为的缺陷，而 AIC 的化学遗传抑制没有效果。我们假设 AIC 的刺激性神经调节可能是一种在阿片类药物滥用中恢复亲社会性的新方法。给动物施用氯氮平-N-氧化物（1.5 毫克/千克，腹腔注射）以评估化学遗传激活或 AIC 抑制的影响。相对于对照动物，AIC 的化学遗传激活逆转了海洛因诱导的拯救行为的缺陷，而 AIC 的化学遗传抑制没有效果。我们假设 AIC 的刺激性神经调节可能是一种在阿片类药物滥用中恢复亲社会性的新方法。