Zhang-James Yanli, Lloyd David R, James Michael L, Yang Lina, Richards Jerry B, Faraone Stephen V
Department of Psychiatry and Behavioral Sciences, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo NY 14203, USA.
J Psychiatr Brain Sci. 2019;4. doi: 10.20900/jpbs.20190021. Epub 2019 Dec 30.
The stimulant, methylphenidate (MPH), is commonly used to treat attention deficit hyperactivity disorder (ADHD) and has been increasingly prescribed for school age children and adolescents. Concerns regarding its long-term effects on later substance use disorders (SUDs) have been raised. Previous animal studies have produced contradictory results regarding whether early exposure to MPH increases or protects against SUD in adulthood. The goal of our study was to determine if clinically relevant doses of MPH during adolescence alter cocaine responsiveness in adulthood in a rat model of ADHD, the spontaneous hypertensive rat (SHR). We pretreated SHRs with saline or MPH (2.5 mg/kg once or twice day) via oral gavage during their dark cycle from postnatal day 35 (p35) to p44. Adult rats (p80) were assessed in an eight-session cocaine-conditioned place preference test (CPP). Four doses of cocaine were administered via intraperitoneal injection (i.p.) during the conditioning sessions: 1, 5, 10 and 20 mg/kg. Once per day MPH treatment had a small sensitizing effect on baseline general locomotor activity in a novel environment at p80 as well as a limited suppressive effect on reward-specific locomotor activity as measured by the decreased preference to enter the cocaine-paired chamber. This treatment did not have any effect on the amount of time that rats chose to spend in the cocaine-paired chamber. Twice per day MPH treatment had no effect on locomotion or drug-preference. Our results suggest that MPH treatment of ADHD rats during adolescence does not alter preference for cocaine in adulthood.
兴奋剂哌甲酯(MPH)常用于治疗注意力缺陷多动障碍(ADHD),且越来越多地被开给学龄儿童和青少年。人们对其对后期物质使用障碍(SUDs)的长期影响表示担忧。先前的动物研究对于早期接触MPH会增加还是预防成年期的SUD产生了相互矛盾的结果。我们研究的目的是确定在ADHD大鼠模型自发性高血压大鼠(SHR)中,青春期给予临床相关剂量的MPH是否会改变成年期对可卡因的反应性。从出生后第35天(p35)至p44的黑暗周期期间,我们通过口服灌胃法用生理盐水或MPH(2.5mg/kg,每天一次或两次)对SHR进行预处理。成年大鼠(p80)在一个八节的可卡因条件性位置偏爱试验(CPP)中接受评估。在条件训练期间,通过腹腔注射(i.p.)给予四剂可卡因:1、5、10和20mg/kg。每天一次的MPH治疗对p80时新环境中的基线总体运动活动有轻微的致敏作用,并且对奖励特异性运动活动有有限的抑制作用,这通过进入与可卡因配对的腔室的偏好降低来衡量。这种治疗对大鼠选择在与可卡因配对的腔室中停留的时间没有任何影响。每天两次的MPH治疗对运动或药物偏好没有影响。我们的结果表明,青春期对ADHD大鼠进行MPH治疗不会改变成年期对可卡因的偏好。