UNASSIGNED: The present study used pharmacological magnetic resonance imaging (phMRI) to evaluate the dose-dependent effect of GAT107 on brain activity in awake male rats. Rats were given a vehicle or one of three different doses of GAT107 (1, 3, and 10 mg/kg) during a 35 min scanning session. Changes in BOLD signal and resting state functional connectivity were evaluated and analyzed using a rat 3D MRI atlas with 173 brain areas.
UNASSIGNED: GAT107 presented with an inverted-U dose response curve with the 3 mg/kg dose having the greatest effect on the positive BOLD volume of activation. The primary somatosensory cortex, prefrontal cortex, thalamus, and basal ganglia, particularly areas with efferent connections from the midbrain dopaminergic system were activated as compared to vehicle. The hippocampus, hypothalamus, amygdala, brainstem, and cerebellum showed little activation. Forty-five min post treatment with GAT107, data for resting state functional connectivity were acquired and showed a global decrease in connectivity as compared to vehicle.
UNASSIGNED: GAT107 activated specific brain regions involved in cognitive control, motivation, and sensory perception using a BOLD provocation imaging protocol. However, when analyzed for resting state functional connectivity there was an inexplicable, general decrease in connectivity across all brain areas.
■本研究使用药理学磁共振成像(phMRI)来评估GAT107对清醒雄性大鼠脑活动的剂量依赖性作用。在35分钟的扫描过程中,向大鼠提供媒介物或三种不同剂量的GAT107(1、3和10mg/kg)之一。使用具有173个脑区域的大鼠3DMRI图谱评估和分析BOLD信号和静息状态功能连通性的变化。
■GAT107呈现倒U剂量反应曲线,其中3mg/kg剂量对激活的阳性BOLD体积具有最大影响。初级体感皮层,前额叶皮质,丘脑,和基底神经节,与媒介物相比,特别是与中脑多巴胺能系统传出连接的区域被激活。海马体,下丘脑,杏仁核,脑干,小脑几乎没有激活。在用GAT107处理后45分钟,获得静息状态功能连通性的数据,并且显示与载体相比,连通性总体降低。
■GAT107激活了参与认知控制的特定大脑区域,动机,和使用BOLD激发成像协议的感官知觉。然而,当分析静息状态功能连通性时,所有大脑区域的连通性普遍下降。