Department of Pharmacy, The Third Affiliated Hospital of Soochow University, The First Peoples's Hospital of Changzhou, 185 Juqian Street, Changzhou, Jiangsu 213003, China; Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588-0308, USA.
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu 210023, China; Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588-0308, USA.
Pharmacol Biochem Behav. 2018 Jun;169:16-26. doi: 10.1016/j.pbb.2018.04.002. Epub 2018 Apr 9.
Previous work suggests that 5-HT receptors play a special role in rodent maternal aggression, but not in other aspects of maternal care (e.g. pup retrieval and nest building). The present study re-assessed the basic effects of 5-HT activation or blockade on various maternal responses in postpartum female rats. We also examined the possible behavioral mechanisms underlying the maternal effects of 5-HT. Sprague-Dawley mother rats were injected with a 5-HT agonist 8-OH-DPAT (0.1, 0.5 or 1.0 mg/kg, sc), a 5-HT antagonist WAY-101405 (0.1, 0.5 or 1.0 mg/kg, sc) or 0.9% saline solution on postpartum days 3, 5, and 7. Maternal behavior was tested 30 min before, 30 min, 120 min, and 240 min after the injection. Acute and repeated 8-OH-DPAT treatment significantly disrupted pup retrieval, pup licking, nursing, and nest building in a dose-dependent fashion, whereas WAY-101405 had no effect at the tested doses. The 5-HT receptor specificity of 8-OH-DPAT's action was confirmed as its maternal disruption effect was reversed by pretreatment of WAY-100635 (a highly selective 5-HT receptor antagonist). Subsequent pup preference test found that 8-OH-DPAT did not decrease the pup preference over a novel object, thus no inhibition on maternal motivation or maternal affect. The pup separation test and pup retrieval on an elevated plus maze test also failed to find any motivational and motor impairment effect with 8-OH-DPAT. However, 8-OH-DPAT at the maternal disruptive dose did disrupt the prepulse inhibition (a measure of attentional function) of acoustic startle response and enhanced the basal startle response. These findings suggest that stimulation of 5-HT receptors by 8-OH-DPAT impairs maternal care by partially interfering with the attentional processing or basal anxiety. More work is needed to further delineate the psychological and neuronal mechanisms underlying the maternal disruptive effect of 5-HT receptor activation.
先前的工作表明，5-HT 受体在啮齿动物的母性行为攻击中发挥特殊作用，但在其他母性行为方面（如幼仔回收和巢穴建造）则没有作用。本研究重新评估了 5-HT 激活或阻断对产后雌性大鼠各种母性行为的基本影响。我们还研究了 5-HT 对母性行为影响的潜在行为机制。在产后第 3、5 和 7 天，给 Sprague-Dawley 母鼠注射 5-HT 激动剂 8-OH-DPAT（0.1、0.5 或 1.0mg/kg，sc）、5-HT 拮抗剂 WAY-101405（0.1、0.5 或 1.0mg/kg，sc）或 0.9%生理盐水。在注射前 30 分钟、注射后 30 分钟、120 分钟和 240 分钟测试母性行为。急性和重复的 8-OH-DPAT 处理以剂量依赖性方式显著破坏了幼仔回收、幼仔舔舐、哺乳和巢穴建造，而 WAY-101405 在测试剂量下没有作用。8-OH-DPAT 作用的 5-HT 受体特异性通过其母体破坏作用被 WAY-100635（一种高度选择性的 5-HT 受体拮抗剂）预处理逆转得到证实。随后的幼仔偏好测试发现，8-OH-DPAT 并没有降低对新物体的幼仔偏好，因此没有抑制母性行为或母性行为的影响。幼仔分离测试和高架十字迷宫测试中的幼仔回收也没有发现 8-OH-DPAT 对动机或运动能力的任何损害作用。然而，在母体破坏剂量下，8-OH-DPAT 确实破坏了声惊跳反应的前脉冲抑制（注意力功能的一种衡量），并增强了基础惊跳反应。这些发现表明，8-OH-DPAT 通过部分干扰注意力加工或基础焦虑来刺激 5-HT 受体，从而损害母性行为。需要进一步的工作来进一步阐明 5-HT 受体激活对母性行为的破坏作用的心理和神经元机制。
