Beneficial and adverse effects of THC on cognition in the HIV-1 transgenic rat model: Importance of exploring task- and sex-dependent outcomes

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity Pub Date : 2025-04-24 DOI:10.1016/j.bbi.2025.04.030

Samantha M. Ayoub , Sunitha Vemuri , Elizabeth B. Hoang , Neal A. Jha , Arpi Minassian , Jared W. Young

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引用次数: 0

Abstract

HIV-associated neurocognitive impairment (NCI) is an untreated concern among people living with HIV (PLWH). Cannabis use in PLWH may complicate outcomes on cognition, with evidence to suggest function-dependent effects that are modulated by several factors including use patterns (e.g., frequency of use) and demographic influences (e.g., age). Animal studies can control for these factors.

Here, we characterized the impact of the primary psychoactive ingredient in cannabis (delta-9-tetrahydrocannabinol; THC), on function-dependent cognitive outcomes in HIV-1 transgenic (Tg) rats using cross-species translatable assays. Female and male HIV-1Tg rats and their controls were tested in the rat Iowa Gambling Task (IGT; to measure risk-based decision-making), and the Probabilistic Reversal Learning Task (PRLT; to measure learning and cognitive flexibility). Rats were tested at baseline, then retested following acute and chronic exposures to THC (0, 0.3, 3 mg/kg, intraperitoneal injection).

At baseline, HIV-1Tg rats took longer to make decisions, but exhibited intact cognition across tasks, suggestive of a speed-accuracy trade-off and early cognitive deficits. Both acute and chronic THC exposures produced selective effects on primary performance measures in HIV-1Tg rats, including enhanced learning performance but worsened risk-based decision-making, not observed in controls.

This work confirms function-dependent effects of THC on cognitive function in an animal model of HIV using cross-species translatable tasks used in the clinic. Findings are consistent with evidence for function-dependent cannabis effects observed in HIV, and suggest THC may drive cannabis-induced changes observed on cognitive performance in PLWH. These data may serve as guidance for clinicians prescribing cannabis to patients with HIV, and for further research exploring the interactive effects of HIV and cannabinoid treatment on cognitive function.

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四氢大麻酚对HIV-1转基因大鼠模型认知的有利和不利影响：探索任务和性别依赖结果的重要性

HIV相关神经认知障碍（NCI）是HIV感染者（PLWH）中未得到治疗的问题。在PLWH中使用大麻可能会使认知结果复杂化，有证据表明，功能依赖性影响受多种因素调节，包括使用模式（如使用频率）和人口影响（如年龄）。动物实验可以控制这些因素。在这里，我们描述了大麻中的主要精神活性成分(δ -9-四氢大麻酚；THC)，对功能依赖的认知结果在HIV-1转基因（Tg）大鼠使用跨物种可翻译的测定。用大鼠爱荷华赌博任务（IGT）测试雌性和雄性HIV-1Tg大鼠及其对照组；以衡量基于风险的决策)，以及概率逆转学习任务(PRLT；以衡量学习和认知灵活性)。大鼠在基线时进行测试，然后在急性和慢性暴露于四氢大麻酚（0,0.3,3 mg/kg，腹腔注射）后重新进行测试。在基线时，HIV-1Tg大鼠需要更长的时间来做决定，但在任务中表现出完整的认知，这表明速度-准确性权衡和早期认知缺陷。急性和慢性四氢大麻酚暴露对HIV-1Tg大鼠的主要表现指标都产生选择性影响，包括学习表现增强，但基于风险的决策恶化，这在对照组中没有观察到。这项工作证实了四氢大麻酚对认知功能的功能依赖作用在一个动物模型的艾滋病毒使用跨物种可翻译的任务在临床使用。研究结果与在HIV中观察到的功能依赖大麻效应的证据一致，并表明四氢大麻酚可能驱动大麻诱导的PLWH认知表现的变化。这些数据可以为临床医生为HIV患者开大麻处方提供指导，并为进一步研究HIV和大麻素治疗对认知功能的相互作用提供指导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain, Behavior, and Immunity 医学-免疫学

CiteScore

29.60

自引率

2.00%

发文量

290

审稿时长

28 days

期刊介绍： Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.