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青少年和成年大鼠自我给药可卡因对刺激-奖赏学习的不同影响。

Differential effects of self-administered cocaine in adolescent and adult rats on stimulus-reward learning.

作者信息

Kerstetter Kerry A, Kantak Kathleen M

机构信息

Laboratory of Behavioral Neuroscience, Department of Psychology, Boston University, 64 Cummington St., Boston, MA 02215, USA.

出版信息

Psychopharmacology (Berl). 2007 Oct;194(3):403-11. doi: 10.1007/s00213-007-0852-6. Epub 2007 Jul 5.

Abstract

RATIONALE

Adult cocaine addicts, abstinent at the time of testing, show a variety of neurocognitive impairments. Less clear is whether there are differences in the degree of impairment if cocaine use is initiated during adolescence rather than adulthood.

OBJECTIVES

Using a preclinical model, we evaluated if stimulus-reward learning was impacted differently in rats exposed to cocaine during adolescence (beginning on postnatal day 37) vs adulthood (beginning on postnatal days 74-79) and then tested after a drug-free period.

MATERIALS AND METHODS

A yoked-triad design of intravenous cocaine self-administration in adult (n = 8 triads) and adolescent (n = 8 triads) rats was used. Sets of three animals either contingently self-administered cocaine or received cocaine or saline in a noncontingent manner. Rats self-administering 1-mg/kg doses of cocaine responded under a fixed-ratio 5, timeout 20-s schedule of reinforcement. After 18 2-h drug or saline sessions, all rats (now adults) began the drug-free period in their home environments. Testing in a stimulus-reward learning task (conditioned cue preference) began 19 days later.

RESULTS

Self-administration behavior was similar in adolescent and adult rats. Lever responses were not significantly different, and both age groups averaged approximately 20 infusions per session. Rats contingently self-administering cocaine or passively exposed to cocaine during adulthood showed stimulus-reward learning deficits in the conditioned cue preference task. Rats exposed to contingent or noncontingent cocaine during adolescence had normal learning, showing strong preferences for a Froot Loops-paired cue.

CONCLUSIONS

These findings suggest that adolescents are insensitive to cocaine-induced impairment of learning related to amygdala memory system functioning.

摘要

理论依据

成年可卡因成瘾者在测试时已戒除毒品,但仍表现出多种神经认知障碍。尚不清楚如果在青春期而非成年期开始使用可卡因,损伤程度是否存在差异。

目的

我们使用一种临床前模型,评估在青春期(从出生后第37天开始)与成年期(从出生后第74 - 79天开始)接触可卡因的大鼠,在经过一段无药期后进行测试时,刺激 - 奖赏学习是否受到不同影响。

材料与方法

采用成年(n = 8组三联体)和青春期(n = 8组三联体)大鼠静脉注射可卡因自我给药的配对三联体设计。每组三只动物,其中一只动物按条件自我给药可卡因,另外两只分别以非条件方式接受可卡因或生理盐水。自我给药1mg/kg剂量可卡因的大鼠在固定比率为5、超时20秒的强化时间表下做出反应。在进行18次2小时的药物或生理盐水给药后,所有大鼠(此时已成年)开始在其家庭环境中进入无药期。19天后开始在刺激 - 奖赏学习任务(条件线索偏好)中进行测试。

结果

青春期和成年大鼠的自我给药行为相似。杠杆反应无显著差异,两个年龄组平均每次给药约20次注射。成年期按条件自我给药可卡因或被动接触可卡因的大鼠在条件线索偏好任务中表现出刺激 - 奖赏学习缺陷。青春期接触条件或非条件可卡因的大鼠学习正常,对与果味圈配对的线索表现出强烈偏好。

结论

这些发现表明,青少年对可卡因引起的与杏仁核记忆系统功能相关的学习损伤不敏感。

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