Department of Psychology, University of Canterbury, Private Bag 4800, Christchurch, New Zealand.
Department of Neuroscience, Psychology and Behaviour, Medical Science Building, University of Leicester, University Road, Leicester LE1 9HN, United Kingdom.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Mar 6;74:1-8. doi: 10.1016/j.pnpbp.2016.11.003. Epub 2016 Nov 16.
A high proportion of young methamphetamine (MA) users simultaneously consume alcohol. However, the potential neurological and behavioural alterations induced by such a drug combination have not been systematically examined. We studied in adolescent rats the long-term effects of alcohol, MA, and alcohol and MA combined on anxiety-like behaviour, memory, and neurogenesis in the adult hippocampus. Rats received saline, ethanol (ETOH, 1.5g/kg), MA (MA, 2mg/kg), or ethanol and MA combined (ETHOH-MA, 1.5g/kg ethanol plus 2mg/kg MA) via oral gavage, once daily for 5 consecutive days. Open field (OF), elevated plus maze (EPM) and radial arm maze (RAM) tests were conducted following a 15-day withdrawal period. The results showed alterations in exploratory behaviour in the OF in the MA and ETOH-MA groups, and anxiety-like effects in the EPM in all three drug treatment groups. All three drug groups exhibited reference memory deficits in the RAM, but only the combination treatment group displayed alterations in working memory. Both MA and ETOH-MA treatments increased the length of doublecortin (DCX)-void gaps in the dentate gyrus but only ETOH-MA treatment increased the number of such gaps. An increased number and length of DCX-void gaps correlated with decreased exploratory activity in the OF, and impaired working memory in the RAM was associated with an augmented number of gaps. These findings suggest that alterations in adult hippocampal neurogenesis are linked to the persistent cognitive and behavioural deficits produced by alcohol and MA exposure.
相当比例的青少年甲基苯丙胺（MA）使用者同时会饮酒。然而，这种药物组合所引起的潜在神经和行为改变尚未得到系统的研究。我们在青少年大鼠中研究了酒精、MA 以及酒精和 MA 联合对成年海马体中焦虑样行为、记忆和神经发生的长期影响。大鼠通过口服灌胃，每天接受一次盐水、乙醇（ETOH，1.5g/kg）、MA（MA，2mg/kg）或乙醇和 MA 联合（ETOH-MA，1.5g/kg 乙醇加 2mg/kg MA），连续 5 天。在 15 天的戒断期后，进行了旷场（OF）、高架十字迷宫（EPM）和放射臂迷宫（RAM）测试。结果显示，MA 和 ETOH-MA 组在 OF 中表现出探索行为的改变，所有三个药物处理组在 EPM 中表现出焦虑样效应。所有三个药物组在 RAM 中都表现出参考记忆缺陷，但只有组合处理组表现出工作记忆的改变。MA 和 ETOH-MA 处理都增加了齿状回中的双皮质素（DCX）空隙的长度，但只有 ETOH-MA 处理增加了这些空隙的数量。DCX 空隙的数量和长度的增加与 OF 中探索活动的减少有关，而 RAM 中工作记忆的损害与空隙数量的增加有关。这些发现表明，成年海马体神经发生的改变与酒精和 MA 暴露所导致的持续认知和行为缺陷有关。
