Alvers Kristin M, Marusich Julie A, Gipson Cassandra D, Beckmann Joshua S, Bardo Michael T
Center for Drug Abuse Research Translation, University of Kentucky, Lexington, Kentucky 40536-0509, USA.
Behav Pharmacol. 2012 Oct;23(7):650-7. doi: 10.1097/FBP.0b013e3283584765.
Despite the efficacy and widespread use of methylphenidate (MPH) as a treatment modality for attention deficit hyperactivity disorder, clinical and preclinical findings indicate that it has abuse potential. Environmental enrichment reduces susceptibility to cocaine and amphetamine self-administration and decreases impulsive behavior, but its effects on MPH self-administration are unknown. The present experiments sought to determine the influence of environmental enrichment on MPH self-administration. Male rats were raised in an enriched condition (EC) or isolated condition (IC). They were trained to self-administer MPH (0.3 mg/kg/infusion) and then exposed to varying doses of MPH on either a fixed-ratio (experiment 1) or a progressive-ratio (experiment 2) schedule of reinforcement. EC rats earned significantly fewer infusions of MPH at low doses (0.03 and 0.056 mg/kg/infusion) compared with IC rats under both schedules; however, no differences were observed at high unit doses (0.1-1.0 mg/kg/infusion). During saline substitution at the end of MPH self-administration, EC rats also responded less for saline compared with IC rats, indicative of more rapid extinction. As with other stimulant drugs with different mechanisms of action, environmental enrichment during development protects against self-administration of MPH at low unit doses but not at high unit doses.
尽管哌甲酯(MPH)作为治疗注意力缺陷多动障碍的一种治疗方式有效且广泛使用,但临床和临床前研究结果表明它具有滥用潜力。环境丰富化可降低对可卡因和苯丙胺自我给药的易感性,并减少冲动行为,但其对MPH自我给药的影响尚不清楚。本实验旨在确定环境丰富化对MPH自我给药的影响。将雄性大鼠饲养在丰富环境(EC)或隔离环境(IC)中。训练它们自我给药MPH(0.3毫克/千克/注射),然后在固定比率(实验1)或累进比率(实验2)强化程序下给予不同剂量的MPH。在两种程序下,与IC大鼠相比,EC大鼠在低剂量(0.03和0.056毫克/千克/注射)时获得的MPH注射显著更少;然而,在高单位剂量(0.1 - 1.0毫克/千克/注射)下未观察到差异。在MPH自我给药结束时进行盐水替代期间,与IC大鼠相比,EC大鼠对盐水的反应也更少,表明消退更快。与其他具有不同作用机制的兴奋剂药物一样,发育期间的环境丰富化可防止低单位剂量的MPH自我给药,但不能防止高单位剂量的MPH自我给药。