Effects of amphetamine exposure in adolescence or young adulthood on inhibitory control in adult male and female rats.
Effects of amphetamine exposure in adolescence or young adulthood on inhibitory control in adult male and female rats.
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DOI：
10.1016/j.bbr.2014.01.015
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发表时间：
2014-04-15
影响因子：
2.7
通讯作者：
Gulley, Joshua M.
中科院分区：
文献类型：
--
作者：
Hammerslag, Lindsey R.;Waldman, Alex J.;Gulley, Joshua M.
冲动性增强是某些精神疾病的特征，包括成瘾，也有性别特异性的表达模式。成瘾和冲动之间的关系可能是由药物诱导的行为变化引起的，这些变化是由内侧前额叶皮层（mPFC）内信号的长期适应引起的。在这里，我们使用了一个反应抑制任务，是敏感的mPFC功能的变化，以检查性别和暴露于安非他明（AMPH）的冲动行为和警惕性的影响。我们还通过注射NMDA受体拮抗剂MK-801（地佐环平）和AMPH来研究药物诱导的多巴胺能和多巴胺能信号传导的改变。将雄性和雌性Sprague道利大鼠注射（i. p.）在青春期（出生后第27-45天（P））或成年期（P85-103），每隔一天给予生理盐水或3 mg/kg AMPH。从P125-135开始，测试大鼠在发出信号的可用性期间杠杆按压以获得食物奖励的能力，以及在“过早反应”阶段期间抑制反应的能力。在实验1中，大鼠接受攻击注射（i. p.）的MK-801和AMPH，随后进行任务表现和运动活动的测试。在实验2中，大鼠接受mPFC内输注MK-801。我们发现，女性有更好的抑制控制和较差的警惕性比男性和AMPH暴露有性别和年龄的暴露依赖性影响冲动。全身性药物挑战扰乱了任务表现，特别是在女性中，并增加了冲动，而内mPFC输注有适度的影响。AMPH暴露不影响对药物挑战的反应。总之，这些结果表明，性别介导的特质和药物诱导的冲动。
Heightened impulsivity is a feature of some psychiatric disorders, including addiction, that also have sex-specific patterns of expression. The relationship between addiction and impulsivity may be driven by drug-induced changes in behavior caused by long term adaptations in signaling within the medial prefrontal cortex (mPFC). Here, we used a response inhibition task that is sensitive to changes in mPFC function to examine the effects of sex and exposure to amphetamine (AMPH) on impulsive action and vigilance. We also examined drug-induced alterations in glutamatergic and dopaminergic signaling through challenge injections with the NMDA receptor antagonist MK-801 (dizocilpine) and AMPH. Male and female Sprague Dawley rats were injected (i.p.) with saline or 3 mg/kg AMPH every other day during adolescence (postnatal day (P) 27–45) or adulthood (P85–103). Starting on P125–135, rats were tested for their ability to lever press for a food reward during periods of signaled availability and withhold responding during a “premature response” phase. In experiment 1, rats received challenge injections (i.p.) of MK-801 and AMPH followed by tests of task performance and locomotor activity. In experiment 2, rats received intra-mPFC infusion of MK-801. We found that females had better inhibitory control and poorer vigilance than males and that AMPH exposure had both sex- and age-of-exposure dependent effects on impulsivity. Systemic drug challenges disrupted task performance, particularly in females, and increased impulsivity while intra-mPFC infusions had modest effects. AMPH exposure did not affect responses to drug challenges. Together, these results suggest that sex mediates both trait and drug-induced impulsivity.
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影响因子：
3.6
作者：
Crews, Fulton Timm;Boettiger, Charlotte Ann
通讯作者：
Boettiger, Charlotte Ann
影响因子：
2.7
作者：
Bayless, Daniel W.;Darling, Jeff S.;Daniel, Jill M.
通讯作者：
Daniel, Jill M.
影响因子：
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作者：
Andersen, SL;Rutstein, M;Teicher, MH
通讯作者：
Teicher, MH
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作者：
Bisagno, V;Ferguson, D;Luine, VN
通讯作者：
Luine, VN
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8.2
作者：
Groman, Stephanie M.;James, Alex S.;Jentsch, J. David
通讯作者：
Jentsch, J. David