Effects of amphetamine exposure during adolescence on behavior and prelimbic cortex neuron activity in adulthood.
Effects of amphetamine exposure during adolescence on behavior and prelimbic cortex neuron activity in adulthood.
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DOI：
10.1016/j.brainres.2018.05.028
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发表时间：
2018-09-01
期刊：
影响因子：
2.9
通讯作者：
Gulley JM
中科院分区：
文献类型：
--
作者：
Sherrill LK;Gulley JM
青春期期间反复接触精神兴奋剂会导致行为发生持久的变化，这可能是由中皮质边缘多巴胺系统发育中断介导的。在这里，我们通过评估安非他明（AMPH）和多巴胺受体选择性药物对内侧前额叶皮质（PFC）前边缘区域的行为和神经元活动的影响来检验这一假设。青春期雄性 Sprague-Dawley 大鼠在出生后第 27 天和第 45 天之间给予盐水或 3 mg/kg AMPH。在实验 1 中，评估了成年期受到多巴胺 D1 (SKF 82958) 或 D2（喹吡罗）受体选择性激动剂挑战后的运动行为。在实验 2 中，预先暴露的大鼠在成年期间接受 AMPH 和 D1 (SKF 83566) 或 D2 (艾氯必利) 受体选择性拮抗剂的攻击。在实验3中，当大鼠在注射AMPH和一种拮抗剂之前和之后在开放场地中表现时，记录了前边缘皮质中假定的锥体细胞的活性。我们发现，与对照组相比，青少年预暴露大鼠对 AMPH 和多巴胺受体激动剂的刺激作用以及拮抗剂逆转 AMPH 诱导的刻板印象的能力更敏感。预先暴露于 AMPH 的大鼠的前缘神经元也更有可能在成年后对 AMPH 挑战做出反应，主要是通过减少其活动，而拮抗剂逆转了这些影响。我们的研究结果表明，青春期暴露于 AMPH 会导致中皮质边缘多巴胺系统的持久适应，这可能会介导成年期对药物的增强反应。
Repeated exposure to psychostimulants during adolescence produces long-lasting changes in behavior that may be mediated by disrupted development of the mesocorticolimbic dopamine system. Here, we tested this hypothesis by assessing the effects of amphetamine (AMPH) and dopamine receptor-selective drugs on behavior and neuron activity in the prelimbic region of the medial prefrontal cortex (PFC). Adolescent male, Sprague-Dawley rats were given saline or 3 mg/kg AMPH between postnatal day (P) 27 and P45. In Experiment 1, locomotor behavior was assessed during adulthood following challenges with a dopamine D1 (SKF 82958) or D2 (quinpirole) receptor-selective agonist. In Experiment 2, pre-exposed rats were challenged during adulthood with AMPH and a D1 (SKF 83566) or D2 (eticlopride) receptor-selective antagonist. In Experiment 3, the activity of putative pyramidal cells in the prelimbic cortex was recorded as rats behaved in an open-field arena before and after challenge injections with AMPH and one of the antagonists. We found that compared to controls, adolescent pre-exposed rats were more sensitive to the stimulant effects of AMPH and the dopamine receptor agonists, as well as to the ability of the antagonists to reverse AMPH-induced stereotypy. Prelimbic neurons from AMPH pre-exposed rats were also more likely to respond to an AMPH challenge in adulthood, primarily by reducing their activity, and the antagonists reversed these effects. Our results suggest that exposure to AMPH during adolescence leads to enduring adaptations in the mesocorticolimbic dopamine system that likely mediate heightened response to the drug during adulthood.
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影响因子：
3.1
作者：
Caballero, Adriana;Flores-Barrera, Eden;Cass, Daryn K.;Tseng, Kuei Y.
通讯作者：
Tseng, Kuei Y.
影响因子：
4.4
作者：
Casaletto, K. B.;Obermeit, L.;Morgan, E. E.;Weber, E.;Franklin, D. R.;Grant, I.;Woods, S. P.
通讯作者：
Woods, S. P.
影响因子：
2.3
作者：
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通讯作者：
Cumming, P
影响因子：
4.7
作者：
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通讯作者：
Di Chiara, Gaetano
影响因子：
3.4
作者：
Horvitz, JC;Williams, G;Joy, R
通讯作者：
Joy, R