Cognitive and Neural Science Program, Department of Psychology, University of South Carolina, Columbia, SC 29208, USA.
Int J Mol Sci. 2022 Aug 13;23(16):9100. doi: 10.3390/ijms23169100.
Independently, chronic cocaine use and HIV-1 viral protein exposure induce neuroadaptations in the frontal-striatal circuit as evidenced by both clinical and preclinical studies; how the frontal-striatal circuit responds to HIV-1 infection following chronic drug use, however, has remained elusive. After establishing experience with both sucrose and cocaine self-administration, a pretest-posttest experimental design was utilized to evaluate preference judgment, a simple form of decision-making dependent upon the integrity of frontal-striatal circuit function. During the pretest assessment, male rats exhibited a clear preference for cocaine, whereas female animals preferred sucrose. Two posttest evaluations (3 days and 6 weeks post inoculation) revealed that, independent of biological sex, inoculation with chimeric HIV (EcoHIV), but not saline, disrupted decision-making. Prominent structural alterations in the frontal-striatal circuit were evidenced by synaptodendritic alterations in pyramidal neurons in the medial prefrontal cortex. Thus, the EcoHIV rat affords a valid animal model to critically investigate how the frontal-striatal circuit responds to HIV-1 infection following chronic drug use.
独立地，慢性可卡因使用和 HIV-1 病毒蛋白暴露会导致额纹状体回路的神经适应，这一点在临床和临床前研究中都得到了证明；然而，在慢性药物使用后，额纹状体回路对 HIV-1 感染的反应仍不清楚。在建立了对蔗糖和可卡因自我给药的经验之后，采用了预测试-后测试实验设计来评估偏好判断，这是一种依赖于额纹状体回路功能完整性的简单形式的决策。在预测试评估中，雄性大鼠表现出对可卡因的明显偏好，而雌性动物则更喜欢蔗糖。两次后测试评估（接种后 3 天和 6 周）表明，与生物性别无关，接种嵌合 HIV（EcoHIV）而不是盐水会破坏决策。在中前额叶皮层的锥体神经元中，突触树突改变证明了额纹状体回路的明显结构改变。因此，EcoHIV 大鼠提供了一个有效的动物模型，可以严格研究在慢性药物使用后，额纹状体回路对 HIV-1 感染的反应。
