Cox Elizabeth Thomas, Jarrett Thomas Merryfield, McMurray Matthew Stephen, Greenhill Kevin, Hofler Vivian E, Williams Sarah Kaye, Joyner Paul Wayland, Middleton Christopher L, Walker Cheryl H, Johns Josephine M
Curriculum in Neurobiology, University of North Carolina at Chapel Hill Chapel Hill, NC, USA.
Front Psychiatry. 2011 Jun 8;2:34. doi: 10.3389/fpsyt.2011.00034. eCollection 2011.
Few systematic studies exist on the effects of chronic reuptake of monoamine neurotransmitter systems during pregnancy on the regulation of maternal behavior (MB), although many drugs act primarily through one or more of these systems. Previous studies examining fluoxetine and amfonelic acid treatment during gestation on subsequent MB in rodents indicated significant alterations in postpartum maternal care, aggression, and oxytocin levels. In this study, we extended our studies to include chronic gestational treatment with desipramine or amitriptyline to examine differential effects of reuptake inhibition of norepinephrine and combined noradrenergic and serotonergic systems on MB, aggression, and oxytocin system changes.
Pregnant Sprague-Dawley rats were treated throughout gestation with saline or one of three doses of either desipramine, which has a high affinity for the norepinephrine monoamine transporter, or amitriptyline, an agent with high affinity for both the norepinephrine and serotonin monoamine transporters. MB and postpartum aggression were assessed on postpartum days 1 and 6 respectively. Oxytocin levels were measured in relevant brain regions on postpartum day 7. Predictions were that amitriptyline would decrease MB and increase aggression relative to desipramine, particularly at higher doses. Amygdaloidal oxytocin was expected to decrease with increased aggression.
Amitriptyline and desipramine differentially reduced MB, and at higher doses reduced aggressive behavior. Hippocampal oxytocin levels were lower after treatment with either drug but were not correlated with specific behavioral effects. These results, in combination with previous findings following gestational treatment with other selective neurotransmitter reuptake inhibitors, highlight the diverse effects of multiple monoamine systems thought to be involved in maternal care.
关于孕期单胺神经递质系统的慢性再摄取对母性行为（MB）调节的影响，目前尚无系统研究，尽管许多药物主要通过这些系统中的一个或多个起作用。先前关于啮齿动物孕期氟西汀和安非他明治疗对后续母性行为影响的研究表明，产后母性护理、攻击性和催产素水平有显著改变。在本研究中，我们将研究扩展至包括孕期使用地昔帕明或阿米替林进行慢性治疗，以检验去甲肾上腺素再摄取抑制以及去甲肾上腺素能和5-羟色胺能系统联合作用对母性行为、攻击性和催产素系统变化的不同影响。
将怀孕的斯普拉格-道利大鼠在整个孕期用生理盐水或三种剂量之一的地昔帕明（对去甲肾上腺素单胺转运体具有高亲和力）或阿米替林（对去甲肾上腺素和5-羟色胺单胺转运体均具有高亲和力）进行治疗。分别在产后第1天和第6天评估母性行为和产后攻击性。在产后第7天测量相关脑区的催产素水平。预测是，相对于地昔帕明，阿米替林会降低母性行为并增加攻击性，尤其是在高剂量时。杏仁核催产素预计会随着攻击性增加而降低。
阿米替林和地昔帕明对母性行为的降低作用不同，且在高剂量时会降低攻击性行为。两种药物治疗后海马体催产素水平均较低，但与特定行为效应无关。这些结果与先前孕期使用其他选择性神经递质再摄取抑制剂后的研究结果相结合，突出了多种单胺系统对母性护理的不同影响。
