Department of Biomedical Sciences Section of Reproduction and Neuroscience, Tufts University, Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Behav Brain Res. 2011 Oct 1;223(2):322-8. doi: 10.1016/j.bbr.2011.04.048. Epub 2011 May 6.
Prior studies have supported a role for mesolimbic dopaminergic mechanisms in the regulation of maternal behavior. Accordingly, the ventral tegmental area (VTA) and its dopaminergic projections to the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in both the onset and maintenance of normal maternal behavior. To date, studies of direct manipulation of VTA neurochemistry at the onset of maternal behavior have been limited. The current study was undertaken to directly test the hypothesis that enhancement of dopaminergic transmission in the mesolimbic dopamine system can stimulate maternal activity using a pup-induced virgin model. Nulliparous female rats were stereotaxically infused with pertussis toxin (PTX 0, 0.1, or 0.3 μg/hemisphere) into the VTA to chronically stimulate the activity of dopaminergic projection neurons. After 3 days of recovery, maternal responding to donor pups was tested daily, and latency (in days) to full maternal behavior was recorded. Intra-VTA PTX treatment produced a robust dose-dependent decrease in maternal behavior latency, and a long-lasting increase in locomotor activity. These effects were associated with significantly decreased dopamine D1 receptor mRNA expression in the NAc. No effects of PTX treatment on mesolimbic dopamine utilization or mPFC receptor expression were observed. The findings indicate that chronic neural activation in the VTA accelerates the onset of maternal behavior in virgin female rats via modification of the NAc dopamine D1 receptor.
先前的研究支持中脑边缘多巴胺能机制在调节母性行为中的作用。因此，腹侧被盖区（VTA）及其多巴胺投射到伏隔核（NAc）和内侧前额叶皮层（mPFC）被认为与正常母性行为的开始和维持有关。迄今为止，关于母性行为开始时 VTA 神经化学的直接操作的研究有限。本研究旨在通过使用诱导的处女模型直接测试这样一个假设，即中脑边缘多巴胺系统中多巴胺传递的增强可以刺激母性行为。将百日咳毒素（PTX 0、0.1 或 0.3μg/半脑）立体定向注入 VTA 中，以慢性刺激多巴胺投射神经元的活性，以此来对处女雌性大鼠进行处理。恢复 3 天后，每天测试母鼠对供体幼崽的反应，并记录完全母性行为的潜伏期（天数）。VTA 内的 PTX 处理产生了母性行为潜伏期的明显剂量依赖性降低，以及运动活动的持久增加。这些影响与 NAc 中多巴胺 D1 受体 mRNA 表达的显著减少有关。PTX 处理对中脑边缘多巴胺利用或 mPFC 受体表达没有影响。这些发现表明，VTA 中的慢性神经激活通过 NAc 中的多巴胺 D1 受体的修饰，加速了处女雌性大鼠母性行为的开始。
