Holschbach M Allie, Vitale Erika M, Lonstein Joseph S
Neuroscience Program, 108 Giltner Hall, Michigan State University, East Lansing, MI, 48824, USA.
Department of Psychology, 108 Giltner Hall, Michigan State University, East Lansing, MI, 48824, USA.
Behav Brain Res. 2018 Aug 1;348:53-64. doi: 10.1016/j.bbr.2018.04.008. Epub 2018 Apr 10.
The behavioral modifications associated with early motherhood, which include high aggression, caring for the young, and low anxiety, are all affected by acute pharmacological manipulation of serotonin signaling. However, the effects on all these behaviors of permanently disrupting serotonin signaling from one of its primary sources, the dorsal raphe nucleus (DR), have not been examined in detail. To address this, serotonin-specific lesions centered on the dorsomedial DR (DRdm; DR subregion strongly implicated in emotional behaviors) were induced at mid-pregnancy (day 15) or early postpartum (day 2) in rats using a saporin-conjugated neurotoxin targeting the serotonin transporter (Anti-SERT-SAP). Prepartum or postpartum Anti-SERT-SAP reduced DRdm serotonin immunoreactivity by ∼40-65%, and postpartum Anti-SERT-SAP also reduced it in the ventromedial and lateral wings of the DR, as well as in the median raphe. Serotonin-immunoreactive fibers were significantly reduced in the anterior hypothalamus, but not medial preoptic area, of lesioned dams. Pre- or postpartum lesions both greatly reduced maternal aggression, but while prepartum lesions did not affect later undisturbed maternal caregiving, the larger postpartum lesions prevented the postpartum decline in kyphotic nursing and reduced pup licking. Serotonin lesions did not affect pup retrieval, but the prepartum lesions temporarily increased maternal hovering over and licking the pups observed immediately after the disruptive retrieval tests. Dams' anxiety-like behaviors and litter weight gains were unaffected by the lesions. These findings suggest that DRdm serotonin projecting to the AH is particularly critical for maternal aggression, but that more widespread disruption of midbrain raphe serotonin is necessary to greatly impair maternal caregiving. Postpartum anxiety may rely more on other neurochemical systems or different midbrain serotonergic cell populations.
与早期为人母相关的行为改变，包括高攻击性、照顾幼崽和低焦虑，均受到血清素信号急性药理学操纵的影响。然而，从其主要来源之一中脑背侧缝核（DR）永久性破坏血清素信号对所有这些行为的影响尚未得到详细研究。为了解决这个问题，在大鼠怀孕中期（第15天）或产后早期（第2天），使用靶向血清素转运体的皂草素偶联神经毒素（抗SERT-SAP），诱导以背内侧DR（DRdm；与情绪行为密切相关的DR亚区域）为中心的血清素特异性损伤。产前或产后抗SERT-SAP使DRdm血清素免疫反应性降低约40-65%，产后抗SERT-SAP还使DR的腹内侧和外侧翼以及中缝核中的血清素免疫反应性降低。在损伤母鼠的下丘脑前部，但不是视前内侧区，血清素免疫反应性纤维显著减少。产前或产后损伤均大大降低了母性攻击性，但产前损伤不影响后期未受干扰的母性照顾，而较大的产后损伤则阻止了产后驼背护理的下降并减少了舔舐幼崽的行为。血清素损伤不影响找回幼崽的行为，但产前损伤会暂时增加母鼠在干扰性找回测试后立即出现的在幼崽上方盘旋和舔舐的行为。损伤对母鼠的焦虑样行为和幼崽体重增加没有影响。这些发现表明，投射到下丘脑前部的DRdm血清素对母性攻击尤为关键，但中脑缝际血清素更广泛的破坏对于严重损害母性照顾是必要的。产后焦虑可能更多地依赖于其他神经化学系统或不同的中脑血清能细胞群。
