McGrath Brent M, McKay Ryan, Dave Sanjay, Seres Peter, Weljie Aalim M, Slupsky Carolyn M, Hanstock Chris C, Greenshaw Andrew J, Silverstone Peter H
Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada T6G 2B7.
Neurosci Res. 2008 Aug;61(4):351-9. doi: 10.1016/j.neures.2008.04.001. Epub 2008 Apr 18.
The pathophysiological underpinnings of bipolar disorder are not fully understood. However, they may be due in part to changes in the phosphatidylinositol second messenger system (PI-cycle) generally, or changes in myo-inositol concentrations more specifically. Dextro-amphetamine has been used as a model for mania in several human studies as it causes similar subjective and physiological symptoms. We wanted to determine if dextro-amphetamine altered myo-inositol concentrations in vivo as it would clearly define a mechanism linking putative changes in the PI-cycle to the subjective psychological changes seen with dextro-amphetamine administration. Fifteen healthy human volunteers received a baseline scan, followed by second scan 75 min after receiving a 25 mg oral dose of dextro-amphetamine. Stimulated echo proton magnetic resonance spectroscopy (MRS) scans were preformed at 3.0 Tesla (T) in the dorsal medial prefrontal cortex (DMPFC). Metabolite data were adjusted for tissue composition and analyzed using LCModel. Twelve adult male rats were treated acutely with a 5-mg/kg intraperitoneal dose of dextro-amphetamine. After 1 h rats were decapitated and the brains were rapidly removed and frozen until dissection. Rat brains were dissected into frontal, temporal, and occipital cortical areas, as well as hippocampus. Tissue was analyzed using a Varian 18.8 T spectrometer. Metabolites were identified and quantified using Chenomx Profiler software. The main finding in the present study was that myo-inositol concentrations in the DMPFC of human volunteers and in the four rat brain regions were not altered by acute dextro-amphetamine. While it remains possible that the PI-cycle may be involved in the pathophysiology of bipolar disorder, it is not likely that the subjective and physiological of dextro-amphetamine are mediated, directly or indirectly, via alternations in myo-inositol concentrations.
双相情感障碍的病理生理基础尚未完全明确。不过，其部分原因可能是磷脂酰肌醇第二信使系统（PI循环）整体发生了变化，或者更具体地说是肌醇浓度发生了变化。在多项人体研究中，右旋苯丙胺被用作躁狂症模型，因为它会引发类似的主观和生理症状。我们想确定右旋苯丙胺是否会在体内改变肌醇浓度，因为这将明确一种机制，将PI循环中假定的变化与服用右旋苯丙胺后出现的主观心理变化联系起来。15名健康人类志愿者接受了一次基线扫描，随后在口服25毫克右旋苯丙胺75分钟后进行了第二次扫描。在3.0特斯拉（T）的条件下，对背内侧前额叶皮质（DMPFC）进行了刺激回波质子磁共振波谱（MRS）扫描。代谢物数据根据组织成分进行了调整，并使用LCModel进行分析。12只成年雄性大鼠被腹腔注射5毫克/千克剂量的右旋苯丙胺进行急性处理。1小时后，将大鼠断头，迅速取出大脑并冷冻直至解剖。将大鼠大脑解剖为额叶、颞叶和枕叶皮质区域以及海马体。使用Varian 18.8 T光谱仪对组织进行分析。使用Chenomx Profiler软件对代谢物进行鉴定和定量。本研究的主要发现是，急性给予右旋苯丙胺后，人类志愿者DMPFC以及大鼠四个脑区的肌醇浓度并未改变。虽然PI循环仍有可能参与双相情感障碍的病理生理过程，但右旋苯丙胺的主观和生理作用不太可能直接或间接通过肌醇浓度的改变来介导。
