Wrenn Craige C, Turchi Janita N, Schlosser Sophie, Dreiling Jennifer L, Stephenson Dejaimenay A, Crawley Jacqueline N
Laboratory of Behavioral Neuroscience, National Institute of Mental Health, Bethesda, MD 20892, USA.
Pharmacol Biochem Behav. 2006 Mar;83(3):428-40. doi: 10.1016/j.pbb.2006.03.003. Epub 2006 Apr 19.
The neuropeptide galanin impairs learning and memory in rodents. The mechanism underlying the cognitive effects of galanin may be related to inhibitory effects of galanin on cholinergic transmission. As cholinergic function is thought to modulate sustained attention, the present study examined whether galanin-overexpressing transgenic mice have impairments in sustained attention. Galanin transgenic (GAL-tg) mice and wild-type (WT) littermate controls were trained in a 5-choice serial reaction time task, modified to assess sustained attention. GAL-tg and WT mice performed similarly during acquisition with respect to accuracy, total omissions, and response speed. Attentional mechanisms were challenged by parametric changes including increased event rate, event asynchrony, or decreased stimulus duration. Singly, these challenges did not differentially affect performance between genotypes. Concurrent administration of these challenges, which represents an optimal test of sustained attention, also had similar effects on GAL-tg and WT mice. When stimulus discriminability was reduced by constant illumination of the house light, GAL-tg mice omitted more trials than WT mice, but other measures of performance did not differ by genotype. Moreover, intraventricular injection of galanin in WT mice did not affect sustained attention. These data indicate that previously reported learning and memory effects of galanin are not secondary to attentional dysfunction.
神经肽甘丙肽会损害啮齿动物的学习和记忆能力。甘丙肽产生认知效应的潜在机制可能与它对胆碱能传递的抑制作用有关。由于胆碱能功能被认为可调节持续注意力，因此本研究检验了过度表达甘丙肽的转基因小鼠在持续注意力方面是否存在缺陷。对甘丙肽转基因（GAL-tg）小鼠和野生型（WT）同窝对照小鼠进行了一项经过改良以评估持续注意力的五选择连续反应时任务训练。在习得过程中，GAL-tg小鼠和WT小鼠在准确性、总遗漏次数和反应速度方面表现相似。通过参数变化（包括增加事件发生率、事件异步性或缩短刺激持续时间）来挑战注意力机制。单独来看，这些挑战对不同基因型小鼠的表现没有差异影响。同时施加这些挑战（这是对持续注意力的最佳测试）对GAL-tg小鼠和WT小鼠也有类似影响。当通过持续照亮室内灯光降低刺激辨别力时，GAL-tg小鼠比WT小鼠遗漏的试验更多，但其他表现指标在不同基因型之间没有差异。此外，向WT小鼠脑室内注射甘丙肽并不影响持续注意力。这些数据表明，先前报道的甘丙肽对学习和记忆的影响并非继发于注意力功能障碍。
