非人灵长类青少年长期接触Δ9-四氢大麻酚:经济需求和大脑功能连接的持续异常。

IF 6.6 1区 医学 Q1 NEUROSCIENCES
Brian D Kangas, Harshawardhan U Deshpande, Sarah L Withey, Roger D Spealman, Jack Bergman, Stephen J Kohut
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引用次数: 0

摘要

虽然青少年时期长期吸食大麻会改变大脑功能并损害复杂的行为过程,但这种缺陷是否会持续到成年还不清楚。为了解决这个问题,我们在非人灵长类动物中采用了一种协调的清醒神经影像学和行为学方法,研究了青少年长期接触Δ9-四氢大麻酚(THC)对成年早期大脑功能连接和动机过程的影响。雌性和雄性松鼠猴(n = 23)在青春期每天接受药物或低剂量(0.32 毫克/千克)或高剂量(3.2 毫克/千克)THC 治疗,为期 6 个月。在长期治疗之前、期间和停止治疗之后,对区域同质性和种子-全脑功能连接性进行了分析,以研究与奖赏处理有关的区域的变化。随后,在经济需求研究中,通过确定不断升级的反应要求与食用不同量级的适口食物强化物之间的关系,对这些受试者(现已成为年轻人)的动机和奖赏敏感性进行了评估。结果表明,青少年时期接触 THC 会导致 mOFC、尾状核和腹侧纹状体全脑连接的持续改变。此外,青春期接受车辆治疗的受试者在奖赏幅度和需求弹性之间表现出一种有序的、预期的反比关系,而接受四氢大麻酚治疗的受试者则在奖赏敏感性和动机缺陷方面表现出剂量依赖性紊乱。神经回路的变化(腹侧纹状体的局部连通性和 mOFC 的全脑连通性)和经济需求与车辆治疗受试者的奖赏敏感性指数相关,但与 THC 治疗受试者无关。综上所述,这些数据表明,青少年长期暴露于 THC 会在奖赏处理过程中产生持久的神经认知异常。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chronic Δ9-tetrahydrocannabinol exposure in adolescent nonhuman primates: persistent abnormalities in economic demand and brain functional connectivity.

Although chronic cannabis use during adolescence can alter brain function and impair complex behavioral processes, it is unclear whether such deficits persist into adulthood. Using a coordinated awake neuroimaging and behavioral approach in nonhuman primates, we addressed this issue by examining the impact of chronic adolescent exposure to Δ9-tetrahydrocannabinol (THC) on brain functional connectivity and motivational processes during early adulthood. Female and male squirrel monkeys (n = 23) were treated daily for 6 months during adolescence with vehicle or either a low (0.32 mg/kg) or high dose (3.2 mg/kg) of THC. Regional homogeneity and seed-to-whole-brain functional connectivity were analyzed prior to, during, and following discontinuation of chronic treatment to examine changes in regions implicated in reward processing. Subsequently, motivation and reward sensitivity in these subjects, now young adults, were evaluated in economic demand studies by determining the relationship between escalating response requirements and consumption of differing magnitudes of a palatable food reinforcer. Results show that adolescent THC exposure led to persistent alterations in mOFC, caudate, and ventral striatum whole-brain connectivity. Moreover, subjects treated with vehicle during adolescence displayed an orderly and expected inverse relationship between reward magnitude and demand elasticity, whereas THC-treated subjects exhibited dosage-dependent disorder in reward sensitivity and motivational deficits. Changes in neural circuitry (local connectivity in ventral striatum and whole brain connectivity in mOFC) and economic demand were correlated with indices of reward sensitivity in vehicle- but not THC-treated subjects. Taken together, these data indicate that chronic adolescent THC exposure produced long-lasting neurocognitive abnormalities in reward processing.

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来源期刊
Neuropsychopharmacology
Neuropsychopharmacology 医学-精神病学
CiteScore
15.00
自引率
2.60%
发文量
240
审稿时长
2 months
期刊介绍: Neuropsychopharmacology is a reputable international scientific journal that serves as the official publication of the American College of Neuropsychopharmacology (ACNP). The journal's primary focus is on research that enhances our knowledge of the brain and behavior, with a particular emphasis on the molecular, cellular, physiological, and psychological aspects of substances that affect the central nervous system (CNS). It also aims to identify new molecular targets for the development of future drugs. The journal prioritizes original research reports, but it also welcomes mini-reviews and perspectives, which are often solicited by the editorial office. These types of articles provide valuable insights and syntheses of current research trends and future directions in the field of neuroscience and pharmacology.
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