In the era of combined antiretroviral therapy, HIV-1 infected individuals are living longer lives; however, longevity is met with an increasing number of HIV-1 associated neurocognitive disorders (HAND) diagnoses. The transactivator of transcription (Tat) is known to mediate the neurotoxic effects in HAND by acting directly on neurons and also indirectly via its actions on glia. The Go/No-Go (GNG) task was used to examine HAND in the Tat transgenic mouse model. The GNG task involves subjects discriminating between two stimuli sets in order to determine whether or not to inhibit a previously trained response. Data reveal inhibitory control deficits in female Tat(+) mice (p = .048) and an upregulation of cannabinoid type 1 receptors (CB₁R) in the infralimbic (IL) cortex in the same female Tat(+) group (p < .05). A significant negative correlation was noted between inhibitory control and IL CB₁R expression (r = −.543, p = .045), with CB₁R expression predicting 30% of the variance of inhibitory control (R² = .295, p = .045). Furthermore, there was a significant increase in spontaneous excitatory postsynaptic current (sEPSC) frequencies in Tat(+) compared to Tat(−) mice (p = .008, across sexes). The increase in sEPSC frequency was significantly attenuated by bath application of PF3845, a fatty acid amide hydrolase (FAAH) enzyme inhibitor (p < .001). Overall, the GNG task is a viable measure to assess inhibitory control deficits in Tat transgenic mice and results suggest a potential therapeutic treatment for the observed deficits with drugs which modulate endocannabinoid enzyme activity.

Results of the Go/No-Go operant conditioning task reveal inhibitory control deficits in female transgenic Tat(+) mice without significantly affecting males. The demonstrated inhibitory control deficits appear to be associated with an upregulation of cannabinoid type 1 receptors (CB₁R) in the infralimbic (IL) cortex in the same female Tat(+) group.

中文翻译：

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与HIV-1 Tat转基因小鼠手模型中CB1R上调相关的抑制性控制缺陷。

在联合抗逆转录病毒疗法的时代，HIV-1感染者的寿命更长；然而，越来越多的HIV-1相关神经认知障碍（HAND）诊断可以满足人们的长寿。已知转录反式激活因子（Tat）通过直接作用于神经元并间接地通过其对神经胶质的作用来介导HAND中的神经毒性作用。Go / No-Go（GNG）任务用于检查Tat转基因小鼠模型中的HAND。GNG任务涉及受试者在两个刺激物之间进行区分，以确定是否抑制先前训练的反应。数据显示雌性Tat（+）小鼠的抑制性控制缺陷（p  = .048）和1型大麻素受体（CB ₁R）在同一雌性Tat（+）组的下肢（IL）皮质中（p  <.05）。抑制性控制与IL CB ₁ R表达之间存在显着的负相关性（r  = -.543，p  = .045），而CB ₁ R表达预测了抑制性控制的30％变异（R ²  = .295，p  = .045）。此外，与Tat（-）小鼠相比，Tat（+）的自发性兴奋性突触后突触电流（sEPSC）频率显着增加（p  = .008，两性之间）。浴中应用脂肪酸酰胺水解酶（FAAH）酶抑制剂PF3845可显着降低sEPSC频率的增加（p <.001）。总体而言，GNG任务是评估Tat转基因小鼠中抑制性控制缺陷的可行措施，结果表明，使用调节内源性大麻素酶活性的药物可对观察到的缺陷进行潜在的治疗。

Go / No-Go操作员调节任务的结果显示了雌性转基因Tat（+）小鼠的抑制性控制缺陷，而对雄性没有明显影响。在同一雌性Tat（+）组中，已证实的抑制性控制缺陷似乎与下肢（IL）皮质中大麻素1型受体（CB ₁ R）的上调有关。