Veterans Administration of Greater Los Angeles System, Los Angeles, California, USA.
Semel Institute and Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, USA.
Int J Neuropsychopharmacol. 2024 Aug 1;27(8). doi: 10.1093/ijnp/pyae031.
The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance.
Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested.
MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus.
Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.
I 型代谢型谷氨酸受体亚型 5（mGlu5）已被牵涉到动物的甲基苯丙胺暴露和人类认知中。由于患有甲基苯丙胺使用障碍（MUD）的人表现出认知缺陷，我们评估了 MUD 患者和对照组中 mGlu5 的情况，并测试了其与认知表现的相关性。
使用正电子发射断层扫描来测量 [18F]FPEB 的总 VT，[18F]FPEB 是 mGlu5 的示踪剂，用于评估 MUD 患者（至少戒断甲基苯丙胺 2 周，N=14）和对照组（N=14）的大脑。我们进行了药物使用史问卷和语言学习、空间工作记忆和执行功能测试。测试了 VT 与甲基苯丙胺使用、烟草使用和认知表现的相关性。
MUD 参与者与对照组在全局或局部 VT 上没有差异，且甲基苯丙胺使用的测量指标与 VT 无关。与吸烟参与者相比，不吸烟参与者的全局 VT 明显更高（主效应，P=0.0041）。MUD 参与者在 Rey 听觉言语学习任务和 Stroop 测试中与对照组相比表现出轻微的弱点（分别为 P=0.08 和 P=0.13），具有中到大的效应大小，并且在空间容量延迟反应测试中明显逊于对照组（P=0.015）。在所有组中， Rey 听觉言语学习任务的表现与背外侧前额叶皮层和额上回的 VT 相关。
戒断的 MUD 患者的大脑中没有显示出 mGlu5 下调的证据，但背外侧前额叶皮层中的 VT 与言语学习相关，这表明靶向 mGlu5 的药物可能改善认知表现。
