Mishra Devesh, Harrison Nicholas R, Gonzales Carolina B, Schilström Björn, Konradsson-Geuken Åsa
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience and Physiology, Section of Neuropsychiatry, Gothenburg University, Gothenburg, Sweden.
PLoS One. 2015 Apr 30;10(4):e0125567. doi: 10.1371/journal.pone.0125567. eCollection 2015.
Ethanol abuse during adolescence may significantly alter development of the prefrontal cortex which continues to undergo structural remodeling into adulthood. Glutamatergic neurotransmission plays an important role during these brain maturation processes and is modulated by ethanol. In this study, we investigated glutamate dynamics in the medial prefrontal cortex of freely moving rats, using enzyme-based microelectrode amperometry. We analyzed the effects of an intraperitoneal ethanol injection (1 g/kg) on cortical glutamate levels in adolescent and adult rats. Notably, basal glutamate levels decreased with age and these levels were found to be significantly different between postnatal day (PND) 28-38 vs PND 44-55 (p<0.05) and PND 28-38 vs adult animals (p<0.001). We also observed spontaneous glutamate release (transients) throughout the recordings. The frequency of transients (per hour) was significantly higher in adolescent rats (PND 28-38 and PND 44-55) compared to those of adults. In adolescent rats, post-ethanol injection, the frequency of glutamate transients decreased within the first hour (p<0.05), it recovered slowly and in the third hour there was a significant rebound increase of the frequency (p<0.05). Our data demonstrate age-dependent differences in extracellular glutamate levels in the medial prefrontal cortex and suggest that acute ethanol injections have both inhibitory and excitatory effects in adolescent rats. These effects of ethanol on the prefrontal cortex may disturb its maturation and possibly limiting individuals´ control over addictive behaviors.
青春期乙醇滥用可能会显著改变前额叶皮质的发育,该区域在成年期仍会持续进行结构重塑。谷氨酸能神经传递在这些大脑成熟过程中起着重要作用,并受到乙醇的调节。在本研究中,我们使用基于酶的微电极安培法,研究了自由活动大鼠内侧前额叶皮质中的谷氨酸动态。我们分析了腹腔注射乙醇(1 g/kg)对青春期和成年大鼠皮质谷氨酸水平的影响。值得注意的是,基础谷氨酸水平随年龄下降,并且在出生后第28 - 38天与第44 - 55天之间(p<0.05)以及出生后第28 - 38天与成年动物之间(p<0.001),这些水平存在显著差异。我们在整个记录过程中还观察到了谷氨酸的自发释放(瞬变)。与成年大鼠相比,青春期大鼠(出生后第28 - 38天和第44 - 55天)的瞬变频率(每小时)显著更高。在青春期大鼠中,乙醇注射后,谷氨酸瞬变频率在第一小时内下降(p<0.05),随后缓慢恢复,在第三小时频率出现显著反弹增加(p<0.05)。我们的数据表明内侧前额叶皮质细胞外谷氨酸水平存在年龄依赖性差异,并表明急性乙醇注射对青春期大鼠具有抑制和兴奋作用。乙醇对前额叶皮质的这些作用可能会干扰其成熟,并可能限制个体对成瘾行为的控制。