Harvey Roxann C, Dembro Kimberly A, Rajagopalan Kiran, Mutebi Michael M, Kantak Kathleen M
Laboratory of Behavioral Neuroscience, Department of Psychology, Boston University, 64 Cummington Street, Boston, MA, 02215, USA.
Psychopharmacology (Berl). 2009 Sep;206(1):61-71. doi: 10.1007/s00213-009-1579-3. Epub 2009 Jun 10.
Deficits in amygdala-related stimulus-reward learning are produced following 18 drug-free days of cocaine self-administration or its passive delivery in rats exposed during adulthood. No deficits in stimulus-reward learning are produced by cocaine exposure initiated during adolescence.
To determine if age of initiating cocaine exposure differentially affects behavioral functioning of an additional memory system linked to cocaine addiction, the orbitofrontal cortex.
A yoked-triad design (n = 8) was used. One rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling drug delivery (1.0 mg/kg) self-administered cocaine from either P37-P59 or P77-P99, and then underwent 18 drug-free days (P60-P77 vs. P100-P117). Rats next were tested for acquisition of odor-delayed win-shift behavior conducted over 15 sessions (P78-P96 vs. P118-P136).
Cocaine self-administration did not differ between adults and adolescents. During the test phase of the odor-delayed win-shift task (relatively difficult task demands), rats from both drug-onset ages showed learning deficits. Rats with cocaine self-administration experience committed more errors and had longer session latencies compared to rats passively receiving saline or cocaine. Rats with adolescent-onset cocaine self-administration experience showed an additional learning deficit by requiring more sessions to reach criterion levels for task acquisition compared to same-aged passive saline controls or rats with adult-onset cocaine self-administration experience. Rats passively receiving cocaine did not differ from the passive saline control from either age group.
Rats with adolescent-onset cocaine self-administration experience were more impaired in an orbitofrontal cortex-related learning task than rats with adult-onset cocaine self-administration experience.
在成年期接触过可卡因的大鼠中，经过18天无药物的可卡因自我给药或被动给药后，会出现与杏仁核相关的刺激-奖励学习缺陷。青春期开始接触可卡因不会导致刺激-奖励学习缺陷。
确定开始接触可卡因的年龄是否会对与可卡因成瘾相关的另一个记忆系统——眶额叶皮层的行为功能产生不同影响。
采用配对三联设计（n = 8）。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。控制药物给药的大鼠（1.0 mg/kg）在P37 - P59或P77 - P99期间自我给药可卡因，然后经历18天无药物期（P60 - P77对P100 - P117）。接下来，对大鼠进行15节次的气味延迟赢者转换行为习得测试（P78 - P96对P118 - P136）。
成年大鼠和青春期大鼠的可卡因自我给药情况没有差异。在气味延迟赢者转换任务的测试阶段（任务要求相对较高），两个药物起始年龄组的大鼠均表现出学习缺陷。与被动接受生理盐水或可卡因的大鼠相比，有可卡因自我给药经历的大鼠犯错误更多，节次潜伏期更长。与同年龄的被动生理盐水对照组或有成年期起始可卡因自我给药经历的大鼠相比，有青春期起始可卡因自我给药经历的大鼠表现出额外的学习缺陷，达到任务习得标准水平需要更多节次。被动接受可卡因的大鼠与两个年龄组的被动生理盐水对照组没有差异。
与有成年期起始可卡因自我给药经历的大鼠相比，有青春期起始可卡因自我给药经历的大鼠在与眶额叶皮层相关的学习任务中受损更严重。
