非授权:目标导向的注意力涉及对行为相关感觉信息的选择性处理。这种选择性处理被认为是由谷氨酸能和去甲肾上腺素能系统支持的。因此,同时靶向这些系统的药物疗法可能是注意力受损的有效治疗方法。
UNASSIGNED:我们首先测试了N-甲基-D-天冬氨酸(NMDA)受体共激动剂(D-丝氨酸)对注意力的影响(处理速度和注意力失误)。NMDA受体激活被认为支持去甲肾上腺素对感觉加工的影响;因此,我们测试了包含D-丝氨酸和去甲肾上腺素再摄取抑制剂(阿托莫西汀)的联合治疗.
UNASSIGNED:首先在执行两种选择的视觉空间区分任务的大鼠中测试D-丝氨酸。然后在单独的组中测试包含相对低剂量的D-丝氨酸和托莫西汀的组合治疗。
UNASSIGNED:在实验1中,D-丝氨酸在测试的最高剂量(300mg/kg)下降低了起始时间(IT)分布(ITdevmode)的偏斜。在实验2中,低剂量D-丝氨酸(125mg/kg)没有影响,而低剂量托莫西汀(0.3mg/kg)可降低ITdevmode并减慢运动速度。重要的是,这些相对低剂量的D-丝氨酸和托莫西汀的组合比单独使用任何一种药物更能降低ITdevmode,而不会进一步减慢运动速度。
未经评估:ITdevmode被认为反映了注意力的失误;因此,D-丝氨酸对ITdevmode的影响表明NMDA受体参与了注意力的准备部署。D-丝氨酸和托莫西汀联合用药后的更大效果表明,同时靶向谷氨酸能和去甲肾上腺素能系统可以促进预备注意力。这些结果可以为患有注意力异常高的ADHD个体提供改进的治疗方法。
Goal-directed attention involves the selective processing of behaviorally relevant sensory information. This selective processing is thought to be supported by glutamatergic and noradrenergic systems. Pharmacotherapies that simultaneously target these systems could therefore be effective treatments for impaired attention.
We first tested an N-methyl-D-aspartate (NMDA) receptor co-agonist (D-serine) for effects on attention (processing speed and attentional lapses). NMDA receptor activation is thought to support noradrenergic effects on sensory processing; therefore, we tested a combination treatment comprising D-serine and a norepinephrine reuptake inhibitor (atomoxetine).
D-serine was first tested in rats performing a two-choice visuospatial discrimination task. Combination treatments comprising relatively low doses of D-serine and atomoxetine were then tested in a separate group.
In experiment 1, D-serine reduced the skew of initiation time (IT) distributions (IT devmode) at the highest dose tested (300 mg/kg). In experiment 2, low-dose D-serine (125 mg/kg) had no effect, while low-dose atomoxetine (0.3 mg/kg) reduced IT devmode and slowed movement speed. Importantly, the combination of these relatively low doses of D-serine and atomoxetine reduced IT devmode more than either drug alone without further slowing movement speed.
IT devmode is thought to reflect attentional lapses; therefore, D-serine\'s effects on IT devmode suggest that NMDA receptors are involved in the preparatory deployment of attention. Greater effects following a combination of D-serine and atomoxetine suggest that preparatory attention can be facilitated by targeting glutamatergic and noradrenergic systems simultaneously. These results could inform the development of improved treatments for individuals with ADHD who experience abnormally high attentional lapses.