Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Departamento de Ciências Morfológicas, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
J Psychopharmacol. 2020 Jul;34(7):750-758. doi: 10.1177/0269881120913153. Epub 2020 Apr 7.
Methylphenidate (MPH) is a stimulant drug mainly prescribed to treat cognitive impairments in attention-deficit/hyperactivity disorder (ADHD). We demonstrated that neonatal hypoxia-ischemia (HI) induced attentional deficits in rats and MPH administration reversed these deficits. However, MPH effects on memory deficits after the HI procedure have not been evaluated yet.
We aimed to analyze learning and memory performance of young hypoxic-ischemic rats after MPH administration and associate their performance with brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex and hippocampus.
Male Wistar rats were divided into four groups (=11-13/group): control saline (CTS), control MPH (CTMPH), HI saline (HIS) and HIMPH. The HI procedure was conducted at post-natal day (PND) 7 and memory tasks between PND 30 and 45. MPH administration (2.5 mg/kg, i.p.) occurred 30 min prior to each behavioral session and daily, for 15 days, for the BDNF assay (=5-7/group).
As expected, hypoxic-ischemic animals demonstrated learning and memory deficits in the novel-object recognition (NOR) and Morris water maze (MWM) tasks. However, MPH treatment did not improve learning and memory deficits of these animals in the MWM-and even disrupted the animals' performance in the NOR task. Increased BDNF levels were found in the hippocampus of HIMPH animals, which seem to have been insufficient to improve memory deficits observed in this group.
The MPH treatment was not able to improve memory deficits resulting from the HI procedure considering a dose of 2.5 mg/kg. Further studies investigating different MPH doses would be necessary to determine a dose-response relationship in this model.
哌醋甲酯（MPH）是一种主要用于治疗注意力缺陷多动障碍（ADHD）认知障碍的兴奋剂药物。我们已经证明，新生大鼠缺氧缺血（HI）会导致注意力缺陷，而 MPH 给药可逆转这些缺陷。然而，MPH 对 HI 后记忆缺陷的影响尚未得到评估。
我们旨在分析接受 MPH 治疗的年轻缺氧缺血大鼠的学习和记忆表现，并将其表现与前额叶皮层和海马体中的脑源性神经营养因子（BDNF）水平相关联。
雄性 Wistar 大鼠分为四组（每组 11-13 只）：生理盐水对照（CTS）、MPH 对照（CTMPH）、HI 生理盐水（HIS）和 HIMPH。HI 程序在出生后第 7 天（PND）进行，记忆任务在 PND 30 至 45 天之间进行。MPH 给药（2.5mg/kg，腹腔注射）在每次行为测试前 30 分钟进行，每日一次，共 15 天，用于 BDNF 测定（每组 5-7 只）。
正如预期的那样，缺氧缺血动物在新物体识别（NOR）和 Morris 水迷宫（MWM）任务中表现出学习和记忆缺陷。然而，MPH 治疗并未改善这些动物在 MWM 中的学习和记忆缺陷，甚至干扰了这些动物在 NOR 任务中的表现。HIMPH 动物的海马体中发现 BDNF 水平升高，但似乎不足以改善该组观察到的记忆缺陷。
考虑到 2.5mg/kg 的剂量，MPH 治疗未能改善 HI 程序引起的记忆缺陷。进一步研究不同 MPH 剂量的治疗效果，对于确定该模型中的剂量反应关系是必要的。
