Jordan Walter T, Minassian Arpi, Perry William, Young Jared W
Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; VA Center of Excellence for Stress and Mental Health, Veterans Administration San Diego HealthCare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
Neurosci Lett. 2022 May 29;780:136639. doi: 10.1016/j.neulet.2022.136639. Epub 2022 Apr 19.
Methamphetamine (METH) use disorder is highly prevalent among people with HIV and is a significant public health problem. Furthermore, people with HIV are living longer and using drugs such as METH even into old age, making it important to understand the effects of METH use and aging in this population. HIV, METH, and aging negatively impact a variety of brain functions, including sensorimotor gating (i.e. - automatic, pre-conscious information processing). Sensorimotor gating is often measured using prepulse inhibition (PPI), a paradigm that can be conducted in animals, thereby allowing for preclinical studies. Little is known about how HIV, METH, and aging interact to affect PPI. The goal of this study was therefore to examine how METH affects PPI in aged gp120 mice, a mouse model of HIV. PPI was measured at 8, 14, and 22 months in male and female wild type (WT) and gp120 mice. PPI was also measured during and after METH treatment at 23-24 months. Aging was associated with decreased PPI in both sexes and genotypes. Combined prior METH treatment and gp120 expression caused the greatest reduction in PPI in aged male mice. Prior METH treatment decreased PPI in aged WT female mice, but not aged gp120 female mice. Overall, these results suggest the effects of HIV and METH on information processing seem to be influenced by age and sex. Combined HIV and METH may impair information processing in older men, but not older women.
甲基苯丙胺(METH)使用障碍在艾滋病毒感染者中极为普遍,是一个重大的公共卫生问题。此外,艾滋病毒感染者的寿命越来越长,甚至到老年仍在使用甲基苯丙胺等毒品,因此了解甲基苯丙胺使用和衰老对这一人群的影响非常重要。艾滋病毒、甲基苯丙胺和衰老会对多种脑功能产生负面影响,包括感觉运动门控(即自动的、意识前的信息处理)。感觉运动门控通常使用前脉冲抑制(PPI)来测量,这是一种可在动物身上进行的范式,从而允许进行临床前研究。关于艾滋病毒、甲基苯丙胺和衰老如何相互作用以影响PPI,人们知之甚少。因此,本研究的目的是研究甲基苯丙胺如何影响老年gp120小鼠(一种艾滋病毒小鼠模型)的PPI。在8、14和22个月时测量雄性和雌性野生型(WT)和gp120小鼠的PPI。在23 - 24个月时,还在甲基苯丙胺治疗期间和治疗后测量PPI。衰老与两性和两种基因型的PPI降低有关。先前甲基苯丙胺治疗和gp120表达的联合作用导致老年雄性小鼠的PPI降低最为显著。先前的甲基苯丙胺治疗使老年WT雌性小鼠的PPI降低,但老年gp120雌性小鼠则不然。总体而言,这些结果表明,艾滋病毒和甲基苯丙胺对信息处理的影响似乎受年龄和性别的影响。艾滋病毒和甲基苯丙胺的联合作用可能会损害老年男性的信息处理能力,但不会损害老年女性的信息处理能力。