Jordan Chloe J, Taylor Danielle M, Dwoskin Linda P, Kantak Kathleen M
Department of Psychological and Brain Sciences, Boston University, Boston, MA 02215, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
Behav Brain Res. 2016 Jan 15;297:165-79. doi: 10.1016/j.bbr.2015.10.017. Epub 2015 Oct 20.
Attention-deficit/hyperactivity disorder (ADHD) is comorbid with cocaine abuse. Whereas initiating ADHD medication in childhood does not alter later cocaine abuse risk, initiating medication during adolescence may increase risk. Preclinical work in the Spontaneously Hypertensive Rat (SHR) model of ADHD found that adolescent methylphenidate increased cocaine self-administration in adulthood, suggesting a need to identify alternatively efficacious medications for teens with ADHD. We examined effects of adolescent d-amphetamine treatment on strategy set shifting performance during adolescence and on cocaine self-administration and reinstatement of cocaine-seeking behavior (cue reactivity) during adulthood in male SHR, Wistar-Kyoto (inbred control), and Wistar (outbred control) rats. During the set shift phase, adolescent SHR needed more trials and had a longer latency to reach criterion, made more regressive errors and trial omissions, and exhibited slower and more variable lever press reaction times. d-Amphetamine improved performance only in SHR by increasing choice accuracy and decreasing errors and latency to criterion. In adulthood, SHR self-administered more cocaine, made more cocaine-seeking responses, and took longer to extinguish lever responding than control strains. Adolescent d-amphetamine did not alter cocaine self-administration in adult rats of any strain, but reduced cocaine seeking during the first of seven reinstatement test sessions in adult SHR. These findings highlight utility of SHR in modeling cognitive dysfunction and comorbid cocaine abuse in ADHD. Unlike methylphenidate, d-amphetamine improved several aspects of flexible learning in adolescent SHR and did not increase cocaine intake or cue reactivity in adult SHR. Thus, adolescent d-amphetamine was superior to methylphenidate in this ADHD model.
注意缺陷多动障碍（ADHD）与可卡因滥用共病。虽然在儿童期开始使用ADHD药物不会改变日后可卡因滥用的风险，但在青少年期开始用药可能会增加风险。在ADHD的自发性高血压大鼠（SHR）模型中的临床前研究发现，青少年使用哌甲酯会增加成年期可卡因的自我给药量，这表明需要为患有ADHD的青少年确定其他有效的药物。我们研究了青少年使用右旋苯丙胺治疗对雄性SHR、Wistar-Kyoto（近交系对照）和Wistar（远交系对照）大鼠在青少年期的策略转换表现以及成年期可卡因自我给药和可卡因觅求行为恢复（线索反应性）的影响。在转换阶段，青少年SHR需要更多的试验次数且达到标准的潜伏期更长，出现更多退行性错误和试验遗漏，并且表现出较慢且更可变的杠杆按压反应时间。右旋苯丙胺仅通过提高选择准确性、减少错误和达到标准的潜伏期来改善SHR的表现。在成年期，SHR比对照品系自我给药更多的可卡因，做出更多的可卡因觅求反应，并且熄灭杠杆反应所需的时间更长。青少年使用右旋苯丙胺并没有改变任何品系成年大鼠的可卡因自我给药量，但减少了成年SHR在七次恢复试验中的第一次试验期间的可卡因觅求行为。这些发现突出了SHR在模拟ADHD中的认知功能障碍和共病可卡因滥用方面的效用。与哌甲酯不同，右旋苯丙胺改善了青少年SHR灵活学习的几个方面，并且没有增加成年SHR的可卡因摄入量或线索反应性。因此，在这个ADHD模型中，青少年使用右旋苯丙胺优于哌甲酯。
