Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Nat Commun. 2021 Aug 9;12(1):4788. doi: 10.1038/s41467-021-25080-x.
Activity in numerous brain regions drives heroin seeking, but no circuits that limit heroin seeking have been identified. Furthermore, the neural circuits controlling opioid choice are unknown. In this study, we examined the role of the infralimbic cortex (IL) to nucleus accumbens shell (NAshell) pathway during heroin choice and relapse. This model yielded subpopulations of heroin versus food preferring rats during choice, and choice was unrelated to subsequent relapse rates to heroin versus food cues, suggesting that choice and relapse are distinct behavioral constructs. Supporting this, inactivation of the IL with muscimol produced differential effects on opioid choice versus relapse. A pathway-specific chemogenetic approach revealed, however, that the IL-NAshell pathway acts as a common limiter of opioid choice and relapse. Furthermore, dendritic spines in IL-NAshell neurons encode distinct aspects of heroin versus food reinforcement. Thus, opioid choice and relapse share a common addiction-limiting circuit in the IL-NAshell pathway.
许多大脑区域的活动驱动着海洛因的寻求，但尚未确定限制海洛因寻求的回路。此外，控制阿片类药物选择的神经回路也是未知的。在这项研究中，我们研究了边缘下皮层（IL）到伏隔核壳（NAshell）通路在海洛因选择和复吸中的作用。该模型在选择期间产生了海洛因与食物偏好的亚种群，而选择与随后对海洛因与食物线索的复吸率无关，这表明选择和复吸是不同的行为结构。支持这一点的是，用 muscimol 失活 IL 对阿片类药物选择与复吸产生了不同的影响。然而，一种通路特异性的化学遗传学方法表明，IL-NAshell 通路是阿片类药物选择和复吸的共同限制因素。此外，IL-NAshell 神经元中的树突棘编码着海洛因与食物强化的不同方面。因此，阿片类药物选择和复吸在 IL-NAshell 通路中共享一个共同的成瘾限制回路。
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