Environmental enrichment alters nicotine-mediated locomotor sensitization and phosphorylation of DARPP-32 and CREB in rat prefrontal cortex.
Environmental enrichment alters nicotine-mediated locomotor sensitization and phosphorylation of DARPP-32 and CREB in rat prefrontal cortex.
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DOI：
10.1371/journal.pone.0044149
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Gomez AM;Midde NM;Mactutus CF;Booze RM;Zhu J
暴露在环境丰富的范例导致神经生物学的适应和减少的基线运动活动。目前的研究确定了DARPP-32（多巴胺和cAMP调节的磷蛋白-32）和CREB（cAMP反应元件结合蛋白）的激活，以及重复给予尼古丁或盐水后在富集（EC），贫困（IC）和标准（SC）条件下饲养的大鼠的运动活动。在生理盐水对照组中，与IC和SC大鼠相比，EC大鼠前额叶皮层（PFC）中DARPP-32 at Thr 34位点（pDARPP-32 Thr 34）的基础磷酸化状态较低，这与其各自的基线活性呈正相关。虽然尼古丁（0.35 mg/kg，游离碱）在所有饲养条件下均产生运动致敏作用，但当尼古丁介导的运动活性表示为相对于其各自生理盐水对照的百分比变化时，EC大鼠对尼古丁的致敏作用大于IC和SC大鼠。与行为学结果一致，重复尼古丁注射增加EC和IC大鼠PFC中的pDARPP-32 Thr 34和EC大鼠的延髓核中的pDARPP-32 Thr 34;然而，相对于IC大鼠，EC大鼠PFC中尼古丁诱导的pDARPP-32 Thr 34增强的变化幅度显著增加。此外，EC大鼠有较低的基础磷酸化水平的CREB在丝氨酸133在PFC和脑桥核相比，IC和SC大鼠，而尼古丁诱导的磷酸化CREB-Ser 133的增加是更明显的PFC的EC大鼠相对于IC和SC大鼠。总的来说，这些研究结果提出了创新的见解，以推进我们对尼古丁激励作用中富集诱导变化的分子机制的理解，并有助于确定烟草吸烟者的新治疗策略。
Exposure within an environmental enrichment paradigm results in neurobiological adaptations and decreases the baseline of locomotor activity. The current study determined activation of DARPP-32 (dopamine- and cAMP-regulated phosphoprotein-32) and CREB (cAMP response element binding protein), and locomotor activity in rats raised in enriched (EC), impoverished (IC), and standard (SC) conditions following repeated administration of nicotine or saline. In the saline-control group, the basal phosphorylation state of DARPP-32 at Threonine-34 site (pDARPP-32 Thr34) in the prefrontal cortex (PFC) was lower in EC compared to IC and SC rats, which was positively correlated with their respective baseline activities. While nicotine (0.35 mg/kg, freebase) produced locomotor sensitization across all housing conditions when the nicotine-mediated locomotor activity was expressed as a percent change from their respective saline control, EC rats displayed greater sensitization to nicotine than IC and SC rats. Consistent with the behavioral findings, repeated nicotine injection increased pDARPP-32 Thr34 in PFC of EC and IC rats and in nucleus accumbens of EC rats; however, the magnitude of change from saline control in nicotine-induced enhancement of pDARPP-32 Thr34 in PFC was strikingly increased in EC rats relative to IC rats. Moreover, EC rats had lower basal phosphorylation levels of CREB at serine 133 in PFC and nucleus accumbens compared to IC and SC rats, whereas the nicotine-induced increase in phosphorylated CREB-Ser133 was more pronounced in PFC of EC rats relative to IC and SC rats. Collectively, these findings suggest innovative insights into advancing our understanding of the molecular mechanisms of enrichment-induced changes in the motivational effects of nicotine, and aiding in the identification of new therapeutic strategies for tobacco smokers.
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影响因子：
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