Alam Nausheen, Choudhary Kulsoom
Federal Urdu University of Arts, Science and Technology, Karachi 75300, Pakistan.
ACS Pharmacol Transl Sci. 2023 Sep 8;6(10):1357-1372. doi: 10.1021/acsptsci.3c00077. eCollection 2023 Oct 13.
Chronic stressful situations result in altered monoaminergic activity of neurotransmitters, resulting in various conditions characterized by deficits in learning, memory and attention. Stimulant effects can be visualized in terms of increased cognitive abilities through enhancement of dopamine (DA) release.
This study examined cognitive responses and brain DA and 5-hydroxytryptamine (5HT) levels after prolonged methylphenidate (MPH) and modafinil administration, to demonstrate their effect on stress-induced cognitive deficits in rats. Effects on cognition were evaluated by passive avoidance and water maze tests. Furthermore brain levels of DA, homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 5HT and 5-hydroxyindoleacetic acid (5HIAA) were analyzed by high-performance liquid chromatography coupled with electrochemical detection.
We found that both MPH and modafinil improved cognition in both restrained and unrestrained rats, as examined through water maze and passive avoidance tests. Furthermore, these substance were associated with increased brain DA and 5-HT levels. Notabily, we observed decrease in DOPAC and HVA levels, while 5-HIAA levels exhibited a slight increase.
The prevention of stress-induced cognitive deficits by MPH and modafinil could be elucidated through the interaction between 5HT and DA in regulating cognitive function.
慢性应激状况会导致神经递质单胺能活性改变，进而引发各种以学习、记忆和注意力缺陷为特征的病症。兴奋剂作用可通过增强多巴胺（DA）释放来提高认知能力得以体现。
本研究检测了长期给予哌醋甲酯（MPH）和莫达非尼后大鼠的认知反应以及脑内DA和5-羟色胺（5HT）水平，以证明它们对应激诱导的大鼠认知缺陷的影响。通过被动回避和水迷宫试验评估对认知的影响。此外，采用高效液相色谱-电化学检测法分析脑内DA、高香草酸（HVA）、二羟基苯乙酸（DOPAC）、5HT和5-羟吲哚乙酸（5HIAA）的水平。
通过水迷宫和被动回避试验检测发现，MPH和莫达非尼均改善了束缚和未束缚大鼠的认知。此外，这些物质与脑内DA和5-羟色胺水平升高有关。值得注意的是，我们观察到DOPAC和HVA水平降低，而5-HIAA水平略有升高。
MPH和莫达非尼对应激诱导的认知缺陷的预防作用可通过5HT和DA在调节认知功能中的相互作用来阐明。
