HIV Transgenic Rats Demonstrate Impaired Sensorimotor Gating But Are Insensitive to Cannabinoid (Δ9-Tetrahydrocannabinol)-Induced Deficits.
HIV Transgenic Rats Demonstrate Impaired Sensorimotor Gating But Are Insensitive to Cannabinoid (Δ9-Tetrahydrocannabinol)-Induced Deficits.
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DOI：
10.1093/ijnp/pyab053
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发表时间：
2021-11-12
期刊：
影响因子：
--
通讯作者：
Young JW
中科院分区：
文献类型：
--
作者：
Roberts BZ;Minassian A;Halberstadt AL;He YV;Chatha M;Geyer MA;Grant I;Young JW
HIV相关的神经认知障碍（HAND）通常在HIV感染者（PWH）中观察到，其特征在于涉及额-纹状体神经回路中断的认知缺陷。这种电路也容易受到大麻和其他滥用药物的影响。PWH使用大麻的比率比一般人群高得多，因此优先考虑艾滋病毒和大麻素之间在认知相关系统上的任何相互作用的特征。惊吓反应的前脉冲抑制（PPI）是对前一个非惊吓刺激的感知减弱对惊吓刺激的运动反应的过程，是一种可跨物种翻译的额纹状体回路完整性的操作测定。PWH的PPI降低。HIV感染的HIV转基因（HIVtg）大鼠模型模拟了HAND的许多方面，尽管迄今为止在PWH中观察到的PPI缺陷尚未在动物中完全重现。在用大麻的主要成分：Δ 9-四氢大麻酚（THC; 1和3 mg/kg，s.c.） 和大麻二酚（1、10和30 mg/kg，i. p.）。相对于野生型对照，HIVtg大鼠表现出显着的PPI缺陷。THC降低了对照组的PPI，但对HIVtg大鼠没有影响。大麻二酚仅对PPI产生轻微的、基因型无关的影响。HIVtg大鼠表现出相对不敏感的THC对PPI所反映的额-纹状体功能的有害影响，这可能部分解释了PWH中大麻使用率较高。
HIV-associated neurocognitive disorder (HAND) is commonly observed in persons living with HIV (PWH) and is characterized by cognitive deficits implicating disruptions of fronto-striatal neurocircuitry. Such circuitry is also susceptible to alteration by cannabis and other drugs of abuse. PWH use cannabis at much higher rates than the general population, thus prioritizing the characterization of any interactions between HIV and cannabinoids on cognitively relevant systems. Prepulse inhibition (PPI) of the startle response, the process by which the motor response to a startling stimulus is attenuated by perception of a preceding non-startling stimulus, is an operational assay of fronto-striatal circuit integrity that is translatable across species. PPI is reduced in PWH. The HIV transgenic (HIVtg) rat model of HIV infection mimics numerous aspects of HAND, although to date the PPI deficit observed in PWH has yet to be fully recreated in animals. PPI was measured in male and female HIVtg rats and wild-type controls following acute, nonconcurrent treatment with the primary constituents of cannabis: Δ 9-tetrahydrocannabinol (THC; 1 and 3 mg/kg, s.c.) and cannabidiol (1, 10, and 30 mg/kg, i.p.). HIVtg rats exhibited a significant PPI deficit relative to wild-type controls. THC reduced PPI in controls but not HIVtg rats. Cannabidiol exerted only minor, genotype-independent effects on PPI. HIVtg rats exhibit a relative insensitivity to the deleterious effects of THC on the fronto-striatal function reflected by PPI, which may partially explain the higher rates of cannabis use among PWH.
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