Charleston Alcohol Research Center, Center for Drug and Alcohol Programs Department of Psychiatry and Behavioral Science, University of South Carolina, Charleston, SC 29425-0742,United States.
Pharmacol Biochem Behav. 2010 May;95(3):267-72. doi: 10.1016/j.pbb.2010.01.009. Epub 2010 Feb 1.
The concomitant use of alcohol (EtOH) and the psychotherapeutic agent dl-methylphenidate (MPH) has risen as a consequence of an increase in ADHD diagnoses within the drinking age population. It was recently found that the combination of MPH and EtOH increases the self-report of pleasurable feelings relative to MPH alone. This finding raises concerns regarding the combined abuse liability for these two widely used drugs. The present behavioral study reports on the development of an adult male C57BL/6J (B6) mouse model to further characterize this MPH-EtOH interaction. We examined the effects of MPH on EtOH consumption in a limited access paradigm and EtOH stimulation of locomotor activity. B6 mice consumed about 2g/kg EtOH daily and MPH dose-dependently reduced drinking. The most effective dose of MPH was 1.25mg/kg, which produced a 41% decrease in drinking and had no effect on locomotor activity. However, when the 1.25mg/kg dose of MPH was combined with a stimulatory dose of ethanol (1.75g/kg) by intraperitoneal injection, there was a significantly enhanced stimulation of locomotor activity. The drug combination increased activity compared to the vehicle or MPH injections by 45% and increased the activity relative to EtOH alone by an additional 25%. The results of the EtOH and MPH interactions observed with the mouse model appear to be behaviorally relevant and suggest several converging mechanisms that may underlie MPH-EtOH interactions.
由于在饮酒年龄人群中多动症的诊断增加，酒精（EtOH）和精神治疗药物右苯丙胺（MPH）的同时使用也有所增加。最近发现，与单独使用 MPH 相比，MPH 和 EtOH 的组合会增加愉悦感的自我报告。这一发现引起了人们对这两种广泛使用的药物联合滥用可能性的关注。本行为研究报告了一种成年雄性 C57BL/6J（B6）小鼠模型的开发，以进一步描述这种 MPH-EtOH 相互作用。我们研究了 MPH 对有限接触范式中 EtOH 消耗的影响以及 EtOH 对运动活性的刺激作用。B6 小鼠每天消耗约 2g/kg EtOH，而 MPH 剂量依赖性地减少了饮酒量。MPH 的最有效剂量为 1.25mg/kg，可使饮酒量减少 41%，对运动活性没有影响。然而，当通过腹腔注射将 1.25mg/kg 剂量的 MPH 与刺激性剂量的乙醇（1.75g/kg）结合使用时，运动活性会显著增强。与载体或 MPH 注射相比，药物组合使活动增加了 45%，与单独使用 EtOH 相比，活动增加了 25%。在小鼠模型中观察到的 EtOH 和 MPH 相互作用的结果似乎具有行为相关性，并提示可能存在几种共同的机制，这些机制可能是 MPH-EtOH 相互作用的基础。
