背景:神经精神疾病如抑郁症的特征部分在于注意力缺陷。注意力由5-羟色胺(5-HT)神经递质系统调节。5-HT2A激动剂和致幻剂psilocybin(PSI)是一种有希望的治疗以注意力变化为特征的疾病的方法。然而,很少有研究调查PSI对注意力的直接影响。
目的:使用啮齿动物连续执行任务(CPT),我们评估了PSI对注意力的影响。为了比较目的,我们还评估了5-HT2A受体激动剂TCB-2和拮抗剂M100907的影响。
方法:在CPT中,小鼠学会了区分视觉目标和非目标的奶昔奖励。然后在注射PSI(0.3、1和3mg/kg)后测试性能,TCB-2(0.3、1和3mg/kg),或M100907(0.1、0.3和1mg/kg)。随后,然后使用具有可变刺激持续时间的更困难的CPT评估药物效果.然后在重复PSI注射后在CPT上测试小鼠。还测量了药物对运动活性的作用。
结果:在CPT中,三种药物均降低了命中和误报率,并引起了保守反应。PSI还减少了目标歧视。这些作用主要在也显著降低运动活性的剂量下观察到。在更困难的CPT或重复PSI注射后未观察到药物作用。
结论:psilocybin,TCB-2和M100907损害了CPT的性能。然而,这可能部分是由于药物引起的运动改变。结果几乎没有支持psilocybin改变视觉注意力的观点,或者5-HT2A受体调节这个过程。
BACKGROUND: Neuropsychiatric disorders such as depression are characterized in part by attention deficits. Attention is modulated by the serotonin (5-HT) neurotransmitter system. The 5-HT2A agonist and hallucinogen psilocybin (PSI) is a promising treatment for disorders characterized by attention changes. However, few studies have investigated PSI\'s direct effect on attention.
OBJECTIVE: Using the rodent continuous performance task (CPT), we assessed PSI\'s effect on attention. We also evaluated the impact of 5-HT2A receptor agonist TCB-2 and antagonist M100907 for comparative purposes.
METHODS: In the CPT, mice learned to distinguish visual targets from non-targets for milkshake reward. Performance was then tested following injections of PSI (0.3, 1, and 3 mg/kg), TCB-2 (0.3, 1, and 3 mg/kg), or M100907 (0.1, 0.3, and 1 mg/kg). Subsequently, drug effects were then evaluated using a more difficult CPT with variable stimulus durations. Mice were then tested on the CPT following repeated PSI injections. Drug effects on locomotor activity were also measured.
RESULTS: In the CPT, all three drugs reduced hit and false alarm rate and induced conservative responding. PSI also reduced target discrimination. These effects were seen primarily at doses that also significantly reduced locomotor activity. No drug effects were seen on the more difficult CPT or following repeated PSI injections.
CONCLUSIONS: Psilocybin, TCB-2, and M100907 impaired performance of the CPT. However, this may be in part due to drug-induced locomotor changes. The results provide little support for the idea that psilocybin alters visual attention, or that 5-HT2A receptors modulate this process.