Dyke Katherine, Pépés Sophia E, Babourina-Brooks Ben, Chen Chen, Kim Soyoung, Sigurdsson Hilmar P, Draper Amelia, Husain Masud, Nachev Parashkev, Gowland Penny, Morris Peter G, Jackson Stephen R
School of Psychology, University of Nottingham, UK.
Sir Peter Mansfield Imaging Centre, University of Nottingham, UK.
Neuroimage Rep. 2021 Feb 5;1(1):100003. doi: 10.1016/j.ynirp.2021.100003. eCollection 2021 Mar.
Gamma-aminobutyric acid (GABA) and glutamate are the primary neurotransmitters responsible for modulating excitatory and inhibitory signalling within the human brain. Dysfunctional GABAergic and glutamatergic signalling has been identified as a key factor in a range of neuropsychiatric conditions; hence measurement and modulation of these neurometabolites is important for improving our understanding of neuropsychiatric conditions and treatment options. Gabapentin (GBP) is one of several drugs developed to increase GABA levels and is routinely prescribed for conditions such as epilepsy and neuralgia. While animal and human studies indicate that GBP can elevate GABA levels, its exact mechanisms of action are not fully understood, although animal studies indicate that GBP does not have a direct effect upon GABAergic receptors. To investigate the impact of acute GBP administration in the human motor system we used two complimentary approaches - transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS). MRS and TMS measures of GABA have repeatedly been found to be uncorrelated and are likely to reflect different pools of synaptic and extra synaptic GABA, hence, measuring both within the same participants allows for an in-depth assessment of GBP effects. Despite significantly increased ratings of fatigue and tiredness within the GBP group, we failed to find any statistically significant changes in our MRS or TMS measures of GABA. Measures of MRS Glutamate (glu) and glutamine (gln) were also not affected by the administration of GBP. These findings are important as they run counter to previous work, and suggest that the effect of an acute dose of GBP is likely to be subject to substantial individual variation, with timing of measures particularly likely to impact observed effects. These findings have implications for the use of acute GBP dosing as a means to explore GABAergic function in health and disease.
γ-氨基丁酸（GABA）和谷氨酸是负责调节人类大脑内兴奋性和抑制性信号传导的主要神经递质。功能失调的GABA能和谷氨酸能信号传导已被确定为一系列神经精神疾病的关键因素；因此，测量和调节这些神经代谢物对于增进我们对神经精神疾病和治疗选择的理解非常重要。加巴喷丁（GBP）是为提高GABA水平而开发的几种药物之一，常用于治疗癫痫和神经痛等疾病。虽然动物和人体研究表明GBP可以提高GABA水平，但其确切作用机制尚未完全了解，尽管动物研究表明GBP对GABA能受体没有直接影响。为了研究急性给予GBP对人体运动系统的影响，我们采用了两种互补的方法——经颅磁刺激（TMS）和磁共振波谱（MRS）。MRS和TMS对GABA的测量结果多次被发现不相关，并且可能反映了不同的突触和突触外GABA池，因此，在同一参与者中同时测量这两者可以深入评估GBP的效果。尽管GBP组的疲劳和疲倦评分显著增加，但我们未能在MRS或TMS对GABA的测量中发现任何统计学上的显著变化。MRS对谷氨酸（glu）和谷氨酰胺（gln）的测量也不受GBP给药的影响。这些发现很重要，因为它们与之前的研究结果相反，并表明急性剂量GBP的效果可能存在很大的个体差异，测量时间尤其可能影响观察到的效果。这些发现对使用急性GBP给药作为探索健康和疾病中GABA能功能的手段具有启示意义。
