Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY 10065, USA; Behavioral and Cognitive Neuroscience Subprogram, Graduate School and University Center, CUNY, 365 Fifth Avenue, New York, NY 10016, USA.
Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY 10065, USA; Behavioral and Cognitive Neuroscience Subprogram, Graduate School and University Center, CUNY, 365 Fifth Avenue, New York, NY 10016, USA.
Brain Res. 2019 May 15;1711:16-22. doi: 10.1016/j.brainres.2019.01.010. Epub 2019 Jan 7.
Methamphetamine is a neurotoxic psychostimulant known to cause cell death and terminal degradation of dopaminergic neurons in the striatum concomitant with memory deficits. However, most of the research studies have not examined the influence of sex on these changes. In this study we compared the effects of a binge regimen of methamphetamine (four injections of 4 mg/kg) on male, female, and ovariectomized (OVX) female Sprague-Dawley rats. We show that male and OVX female animals had a deficit in a novel object recognition task, while intact females did not show this deficit. Neurochemical analysis of the same animals indicated higher levels of FosB protein in caudate-putamen (CPu) and nucleus accumbens (NAc) of the male animals than intact or OVX females. Methamphetamine also increased Bcl-2 protein levels in CPu of all the cohorts. We did not find a significant effect of methamphetamine on the dopamine neuron markers tyrosine hydroxylase (TH) or dopamine transporter (DAT) 7 days after methamphetamine administrations. Our behavioral and neurochemical studies indicate that methamphetamine differentially affects male and female animals and shows sex differences in memory and molecular mechanisms in the striatum of these animals.
甲基苯丙胺是一种神经毒性的精神兴奋剂，已知会导致纹状体中的多巴胺能神经元死亡和终末退化，同时伴随记忆缺陷。然而，大多数研究并未研究性别对这些变化的影响。在这项研究中，我们比较了一次大量吸食（四次注射 4mg/kg）甲基苯丙胺对雄性、雌性和去卵巢（OVX）雌性 Sprague-Dawley 大鼠的影响。我们发现雄性和 OVX 雌性动物在新物体识别任务中存在缺陷，而完整的雌性动物则没有表现出这种缺陷。对同一批动物的神经化学分析表明，雄性动物的尾壳核（CPu）和伏隔核（NAc）中的 FosB 蛋白水平高于完整或 OVX 雌性动物。甲基苯丙胺还增加了所有组 CPu 中的 Bcl-2 蛋白水平。我们没有发现甲基苯丙胺对多巴胺神经元标志物酪氨酸羟化酶（TH）或多巴胺转运体（DAT）的显著影响，在甲基苯丙胺给药 7 天后。我们的行为和神经化学研究表明，甲基苯丙胺对雄性和雌性动物有不同的影响，并显示出这些动物纹状体在记忆和分子机制方面的性别差异。
