Nuclear Medicine and PET-Center, Aarhus University Hospital, Aarhus, Denmark.
Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark.
Brain Behav. 2019 Mar;9(3):e01239. doi: 10.1002/brb3.1239. Epub 2019 Feb 20.
We have previously shown that an interaction between medial prefrontal and parietal cortices is instrumental in promoting self-awareness via synchronizing oscillations in the gamma range. The synchronization of these oscillations is modulated by dopamine release. Given that such oscillations result from intermittent GABA stimulation of pyramidal cells, it is of interest to determine whether the dopaminergic system regulates GABA release directly in cortical paralimbic regions. Here, we test the hypothesis that the regulation of the GABA-ergic system by the dopaminergic system becomes attenuated in problem gamblers resulting in addictive behaviors and impaired self-awareness.
[ C]Ro15-4513 PET, a marker of benzodiazepine α1/α5 receptor availability in the GABA receptor complex, was used to detect changes in synaptic GABA levels after oral doses of 100mg L-dopa in a double-blind controlled study of male problem gamblers (N = 10) and age-matched healthy male controls (N = 10).
The mean reduction of cortical gray matter GABA/BDZ receptor availability induced by L-dopa was significantly attenuated in the problem gambling group compared to the healthy control group (p = 0.0377).
Our findings demonstrate that: (a) Exogenous dopamine can induce synaptic GABA release in healthy controls. (b) This release is attenuated in frontal cortical areas of males suffering from problem gambling, possibly contributing to their loss of inhibitory control. This suggests that dysfunctional dopamine regulation of GABA release may contribute to problem gambling and gambling disorder.
我们之前已经表明，内侧前额叶和顶叶皮质之间的相互作用通过同步伽马范围内的振荡在促进自我意识方面起着重要作用。这些振荡的同步受到多巴胺释放的调节。鉴于这些振荡是由于 GABA 间歇性刺激锥体细胞而产生的，因此有必要确定多巴胺系统是否直接调节皮质边缘区域的 GABA 释放。在这里，我们测试了这样一个假设，即多巴胺系统对 GABA 能系统的调节在问题赌徒中减弱，导致成瘾行为和自我意识受损。
[C] Ro15-4513 PET，是 GABA 受体复合物中苯二氮䓬 α1/α5 受体可用性的标志物，用于在男性问题赌徒（N=10）和年龄匹配的健康男性对照组（N=10）的双盲对照研究中检测口服 100mg L-多巴后突触 GABA 水平的变化。
与健康对照组相比，L-多巴诱导的皮质灰质 GABA/BDZ 受体可用性的平均降低在问题赌博组中明显减弱（p=0.0377）。
我们的研究结果表明：（a）外源性多巴胺可以诱导健康对照者的突触 GABA 释放。（b）这种释放在前额皮质区域的男性问题赌博者中减弱，可能导致他们抑制控制的丧失。这表明，多巴胺对 GABA 释放的功能障碍调节可能导致问题赌博和赌博障碍。
