The prefrontal cortex (PFC) is involved in complex planning, learning, memory, attention and integrates sensory information. It was reported that the PFC was dysfunctional in attention deficit hyperactivity disorder (ADHD). Methylphenidate (MPD), a drug often prescribed for the treatment of ADHD, has potential for abuse and misuse. Most MPD studies were completed in adult subjects;however, most users were adolescents. The objective of this study was to investigate the acute and chronic dose response characteristics of MPD on PFC neuronal activity recorded in freely behaving adolescent rats. Four groups of animals were used: saline (control), 0.6, 2.5, and 10 mg/kg MPD. Acute MPD elicited a dose response increase in animals’ locomotor activity. Rechallenge with MPD at experimental day (ED10) when compared to the effect of MPD at ED1 showed no significant differences. When the animals were divided into two groups based on their individual responses to chronic MPD exposure, some animals expressed behavioral tolerance and some expressed behavioral sensitization. Electrophysiologically, a dose response characteristic for acute and chronic MPD exposure was observed. With increasing MPD doses, more PFC units responded by changing their firing rate. Moreover, the neuronal responses to chronic MPD recorded from animals expressing behavioral tolerance were significantly different compared to the neuronal population responses recorded from animals expressing behavioral sensitization. The majority of the PFC units recorded from animals expressing behavioral tolerance responded to MPD predominately by decreasing their firing rates, whereas PFC units recorded from behaviorally sensitized animals mainly showed an increase in their firing rates.
目的:评价小儿智力糖浆治疗儿童注意缺陷多动障碍(ADHD)的疗效和安全性。方法:制定原始文献的纳入标准及检索策略,计算机检索Cochr ane Li br ar y、Pub Med、中国生物医学数据库(CBM)、中国期刊全文数据库(CNKI)、万方数据库(Wanf ang dat a)和维普数据库(Vi p),收集小儿智力糖浆与利他林治疗儿童注意缺陷多动障碍的随机对照试验(RCT),检索时限均为2000年4月—2014年4月。按纳入和排除标准筛选试验、提取资料并评价研究质量后,用Rev Man 5.2软件进行统计学分析。结果:最终纳入8个随机对照试验,共764例ADHD患儿。Met a分析结果显示:小儿智力糖浆组总有效率[RR=1.17,95%CI(1.05,1.31)]、近期临床显效率[RR=1.20,95%CI(1.04,1.39)]、不良反应发生率[RR=0.16,95%CI(0.11,0.26)]与利他林组比较,差异均具有统计学意义(P<0.05)。多动指数[MD=-0.03,95%CI(-0.14,0.07)],2组间差异无统计学意义。所有纳入研究均报道小儿智力糖浆无严重不良反应。结论:目前证据表明,小儿智力糖浆治疗儿童注意缺陷多动障碍的总有效率、近期临床显效率等方面明显优于利他林;不良反应发生率小儿智力糖浆组显著低于利他林组、安全性高。由于纳入研究数量限制,上述结论尚需进一步开展更多高质量、大样本RCT加以验证。
Methylphenidate (MPD), known as Ritalin, is a common drug prescribed for those diagnosed with Attention Deficit Hyperactivity Disorder (ADHD).There are reports that many MPD users consume alcohol, resulting in toxic effects and hospitalization. The goal of this study was to investigate the effects of ethanol in rats concomitant with acute and repetitive MPD exposure. Rats were divided into four groups, control (saline), 0.6 mg/kg MPD, 2.5 mg/kg MPD, and 10.0 mg/kg MPD groups and lasted for 12 consecutive days. Ethanol was given after repeated MPD administration as follows. On experimental day 1 (ED 1), all animals were treated with saline to establish baseline, on ED 2 through ED 7 either saline or MPD (0.6, 2.5, or 10.0 mg/kg) was given. On ED 11, after three days without treatment (ED 8 - 10), rats were treated as they were on ED 2 - 7. At ED 12, 1 g/kg ethanol was administered, and one hour of locomotor activity was recorded after alcohol administration, using the open field assay. The data show a dose response characteristic of increased locomotor activity with increasing doses of MPD. Ethanol administration alone depresses locomotor activity. The depressive effect of alcohol was significantly attenuated in animals treated with MPD, in a dose dependent manner. The higher dose of MPD previously administered resulted in a larger attenuation of the ethanol’s suppressive effect. These trends demonstrate that chronic MPD exposure directly influences the effects of alcohol in rats. Under these circumstances, it is reasonable to assume that a subject will need to consume an increased amount of ethanol in order to attain the ethanol effect desired. This discrepancy between effects and exposure may be a liability for ethanol toxicity.
