Kantak Kathleen M, Barlow Nicole, Tassin David H, Brisotti Madeline F, Jordan Chloe J
Department of Psychological and Brain Sciences, Boston University, 64 Cummington Mall, Boston, MA, 02215, USA,
Psychopharmacology (Berl). 2014 Dec;231(23):4489-501. doi: 10.1007/s00213-014-3598-y. Epub 2014 May 7.
Neuropsychological testing is widespread in adult cocaine abusers, but lacking in teens. Animal models may provide insight into age-related neuropsychological consequences of cocaine exposure.
The objective of the present study is to determine whether developmental plasticity protects or hinders behavioral flexibility after cocaine exposure in adolescent vs. adult rats.
Using a yoked-triad design, one rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling cocaine delivery (1.0 mg/kg) self-administered for 18 sessions (starting P37 or P77), followed by 18 drug-free days. Rats next were tested in a strategy set shifting task, lasting 11-13 sessions.
Cocaine self-administration did not differ between age groups. During initial set formation, adolescent-onset groups required more trials to reach criterion and made more errors than adult-onset groups. During the set shift phase, rats with adult-onset cocaine self-administration experience had higher proportions of correct trials and fewer perseverative + regressive errors than age-matched yoked-controls or rats with adolescent-onset cocaine self-administration experience. During reversal learning, rats with adult-onset cocaine experience (self-administered or passive) required fewer trials to reach criterion, and the self-administering rats made fewer perseverative + regressive errors than yoked-saline rats. Rats receiving adolescent-onset yoked-cocaine had more trial omissions and longer lever press reaction times than age-matched rats self-administering cocaine or receiving yoked-saline.
Prior cocaine self-administration may impair memory to reduce proactive interference during set shifting and reversal learning in adult-onset but not adolescent-onset rats (developmental plasticity protective). Passive cocaine may disrupt aspects of executive function in adolescent-onset but not adult-onset rats (developmental plasticity hinders).
神经心理学测试在成年可卡因滥用者中广泛应用,但在青少年中却很少见。动物模型可能有助于深入了解可卡因暴露与年龄相关的神经心理学后果。
本研究的目的是确定发育可塑性在青少年和成年大鼠可卡因暴露后对行为灵活性是起到保护作用还是阻碍作用。
采用配对三联设计,一只大鼠控制可卡因给药,另外两只被动接受可卡因或生理盐水。控制可卡因给药的大鼠(1.0毫克/千克)自我给药18次(从第37天或第77天开始),随后是18天的无药期。接下来,大鼠在一个策略集转换任务中接受测试,该任务持续11 - 13次试验。
不同年龄组的可卡因自我给药情况没有差异。在初始集形成阶段,青春期开始组比成年期开始组需要更多的试验次数才能达到标准,并且犯错更多。在集转换阶段,有成年期开始可卡因自我给药经历的大鼠比年龄匹配的配对对照组或有青春期开始可卡因自我给药经历的大鼠有更高比例的正确试验次数和更少的持续性 + 退行性错误。在反转学习过程中,有成年期开始可卡因经历(自我给药或被动给药)的大鼠达到标准所需的试验次数更少,并且自我给药的大鼠比配对生理盐水组大鼠的持续性 + 退行性错误更少。接受青春期开始配对可卡因的大鼠比年龄匹配的自我给药可卡因或接受配对生理盐水的大鼠有更多的试验遗漏和更长的杠杆按压反应时间。
先前的可卡因自我给药可能会损害记忆,以减少成年期开始而非青春期开始的大鼠在集转换和反转学习过程中的主动干扰(发育可塑性起保护作用)。被动给予可卡因可能会破坏青春期开始而非成年期开始的大鼠的执行功能方面(发育可塑性起阻碍作用)。