Wrubel Kathryn M, Riha Penny D, Maldonado Monica A, McCollum David, Gonzalez-Lima F
Department of Psychology, University of Texas at Austin, Austin, TX 78712, USA.
Pharmacol Biochem Behav. 2007 Apr;86(4):712-7. doi: 10.1016/j.pbb.2007.02.018. Epub 2007 Mar 6.
Methylene blue (MB) is a metabolic enhancer that has been demonstrated to improve memory retention when given post-training in low doses in a variety of tasks in rats, including inhibitory avoidance, spatial memory (in both normal and metabolically-impaired subjects), object recognition, and habituation to a familiar environment. MB has been also shown to improve memory retention of extinction of fear conditioning in the rat. No experiments have been conducted to determine the effects of MB on more complex learning such as in discrimination tasks that require repeated days of training. This study examined the effects of daily MB on spatial discrimination memory in a baited holeboard maze. Following three days of discrimination training, subjects treated daily with post-training MB (1 mg/kg) reliably discriminated between rewarded (baited) and non-rewarded (unbaited) trials as indicated by a greater number of correct responses on rewarded trials than non-rewarded trials during the last three days of discrimination training. No such discrimination effects were observed in the saline-treated control group during the same training period. To determine whether the memory-enhancing effects of MB are associated with an increase in metabolic energy capacity in the brain, cytochrome c oxidation was measured in brains from rats treated with 1 mg/kg MB or saline for three days. The number of daily injections was chosen based on the behavioral data which revealed group differences three days after the beginning of MB treatment. Brain cytochrome oxidase activity in the MB-treated group was approximately 70% higher than in saline-treated rats. The findings suggest that repeated post-training MB may improve memory consolidation between days of learning by an induction in the enzyme cytochrome oxidase, leading to increased metabolic capacity in brain regions requiring more energy during discrimination learning.
亚甲蓝（MB）是一种代谢增强剂，已证明在大鼠的多种任务中，训练后给予低剂量的亚甲蓝可改善记忆保持，这些任务包括抑制性回避、空间记忆（在正常和代谢受损的受试者中）、物体识别以及对熟悉环境的习惯化。亚甲蓝还被证明可改善大鼠恐惧条件反射消退的记忆保持。尚未进行实验来确定亚甲蓝对更复杂学习的影响，例如在需要多天训练的辨别任务中。本研究考察了每日给予亚甲蓝对带饵孔板迷宫中空间辨别记忆的影响。在进行三天的辨别训练后，每天训练后接受亚甲蓝（1毫克/千克）治疗的受试者能够可靠地区分奖励（有饵）和无奖励（无饵）试验，这表现为在辨别训练的最后三天中，奖励试验的正确反应次数比无奖励试验更多。在同一训练期间，生理盐水处理的对照组未观察到这种辨别效应。为了确定亚甲蓝的记忆增强作用是否与大脑代谢能量能力的增加有关，对用1毫克/千克亚甲蓝或生理盐水处理三天的大鼠大脑中的细胞色素c氧化进行了测量。根据行为数据选择每日注射次数，行为数据显示在亚甲蓝治疗开始三天后出现组间差异。亚甲蓝治疗组的脑细胞色素氧化酶活性比生理盐水处理的大鼠高约70%。研究结果表明，重复训练后给予亚甲蓝可能通过诱导细胞色素氧化酶来改善学习期间各天之间的记忆巩固，从而导致在辨别学习期间需要更多能量的脑区代谢能力增加。
