Fentanyl-induced changes in brain activity in awake nonhuman primates at 9.4 Tesla.
Fentanyl-induced changes in brain activity in awake nonhuman primates at 9.4 Tesla.
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芬太尼在 9.4 特斯拉时会引起清醒的非人类灵长类动物大脑活动的变化。
DOI：
10.1007/s11682-022-00639-4
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发表时间：
2022
影响因子：
3.2
通讯作者：
Kohut,StephenJ
中科院分区：
文献类型：
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作者：
Withey,SarahL;Cao,Lei;deMoura,FernandoB;Cayetano,KenroyR;Rohan,MichaelL;Bergman,Jack;Kohut,StephenJ
功能性磁共振成像（fMRI）已被用于研究阿片类药物对涉及阿片类药物使用障碍的神经回路的影响，如皮质-纹状体-丘脑-皮质（CSTC）回路。鉴于芬太尼相关死亡人数的增加，本研究旨在描述芬太尼对清醒的非人类灵长类动物大脑激活模式的影响。四只松鼠猴适应了9.4特斯拉的清醒扫描程序。随后，进行了测试，给药剂量为1 μg/kg的芬太尼可可靠地维持猴子的静脉（IV）自我给药行为，并使用以下方法评估对脑活动模式的影响：(1)阐明芬太尼诱导的神经活动模式的药理学回归因子；(2)针对双侧前扣带、丘脑或伏隔核（NAc）的基于种子的方法，以确定CSTC功能连接的改变。结果显示，在阿片激动剂介导行为效应的脑区，如扣带皮层、纹状体和中脑，BOLD信号受到功能性抑制。每个种子区与涉及运动、感觉和认知相关行为的区域之间的功能连通性普遍下降。相反，NAc与其他纹状体区域的功能连通性增加。这些结果表明，芬太尼在CSTC回路中产生的变化可能反映了阿片类药物使用障碍的关键特征（例如持续吸毒/寻求药物），从而导致行为和成瘾的长期中断。他们还指出，警觉的非人类灵长类动物的功能磁共振成像可以检测到药物引起的神经回路变化，反过来，可能有助于研究药物逆转药物引起的失调的有效性。
Functional magnetic resonance imaging (fMRI) has been used to study the influence of opioids on neural circuitry implicated in opioid use disorder, such as the cortico-striatal-thalamo-cortical (CSTC) circuit. Given the increase in fentanyl-related deaths, this study was conducted to characterize the effects of fentanyl on patterns of brain activation in awake nonhuman primates. Four squirrel monkeys were acclimated to awake scanning procedures conducted at 9.4 Tesla. Subsequently, test sessions were conducted in which a dose of fentanyl that reliably maintains intravenous (IV) self-administration behavior in monkeys, 1 μg/kg, was administered and the effects on patterns of brain activity were assessed using: (1) a pharmacological regressor to elucidate fentanyl-induced patterns of neural activity, and (2) seed-based approaches targeting bilateral anterior cingulate, thalamus, or nucleus accumbens (NAc) to determine alterations in CSTC functional connectivity. Results showed a functional inhibition of BOLD signal in brain regions that mediate behavioral effects of opioid agonists, such as cingulate cortex, striatum and midbrain. Functional connectivity between each of the seed regions and areas involved in motoric, sensory and cognition-related behavior generally decreased. In contrast, NAc functional connectivity with other striatal regions increased. These results indicate that fentanyl produces changes within CSTC circuitry that may reflect key features of opioid use disorder (e.g. persistent drug-taking/seeking) and thereby contribute to long-term disruptions in behavior and addiction. They also indicate that fMRI in alert nonhuman primates can detect drug-induced changes in neural circuits and, in turn, may be useful for investigating the effectiveness of medications to reverse drug-induced dysregulation.