Henry Brook L, Geyer Mark A, Buell Mahalah R, Perry William, Young Jared W, Minassian Arpi
aDepartment of Psychiatry, University of California, San Diego bResearch Service, VA San Diego Healthcare System cCenter of Excellence for Stress and Mental Health, (CESAMH), Veteran's Administration, San Diego, California, USA.
Behav Pharmacol. 2014 Feb;25(1):12-22. doi: 10.1097/FBP.0000000000000012.
HIV infection is frequently comorbid with methamphetamine (METH) dependence. Both factors are associated with impairment in inhibitory function that continues even after abstinence from the drug. Deficits in prepulse inhibition (PPI), a measure of sensorimotor gating, are induced by acute stimulant administration, but the combined effect of HIV and chronic METH exposure on PPI is not well characterized. We quantified baseline acoustic startle and PPI in mice expressing the HIV-1 gp120 envelope protein (gp120tg) and in wild-type (WT) littermates; thereafter, we administered a chronic regimen of METH or vehicle and tested startle and PPI after 7 days of drug withdrawal. We hypothesized that METH-treated gp120tg mice would exhibit PPI deficits compared with vehicle-treated WT or gp120tg animals. Before METH administration, drug-naive female gp120tg mice exhibited decreased PPI compared with female WT mice, whereas male gp120tg mice exhibited increased startle compared with other groups. After drug withdrawal, no consistent genotype effect was observed, but METH-treated mice exhibited increased PPI compared with vehicle, in contrast to previous reports of acute METH-induced PPI deficits. In summary, PPI impairment in HIV could depend on factors such as sex, whereas changes in PPI following METH withdrawal may depend on the quantity and duration of drug exposure.
HIV感染常与甲基苯丙胺（METH）依赖并存。这两个因素都与抑制功能受损有关，即使在戒毒后这种损害仍会持续。前脉冲抑制（PPI）是一种感觉运动门控的测量指标，急性给予兴奋剂会导致其缺陷，但HIV和慢性METH暴露对PPI的联合影响尚未得到充分表征。我们对表达HIV-1 gp120包膜蛋白（gp120tg）的小鼠和野生型（WT）同窝小鼠的基线听觉惊吓和PPI进行了量化；此后，我们给予METH或赋形剂的慢性给药方案，并在停药7天后测试惊吓和PPI。我们假设，与给予赋形剂的WT或gp120tg动物相比，接受METH治疗的gp120tg小鼠会表现出PPI缺陷。在给予METH之前，未接触过药物的雌性gp120tg小鼠与雌性WT小鼠相比，PPI降低，而雄性gp120tg小鼠与其他组相比，惊吓增加。停药后，未观察到一致的基因型效应，但与赋形剂相比，接受METH治疗的小鼠PPI增加，这与之前关于急性METH诱导PPI缺陷的报道相反。总之，HIV中的PPI损害可能取决于性别等因素，而METH戒断后PPI的变化可能取决于药物暴露的量和持续时间。
