Zhang T Y, Chrétien P, Meaney M J, Gratton A
Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montréal, Québec, H4H 1R3 Canada.
J Neurosci. 2005 Feb 9;25(6):1493-502. doi: 10.1523/JNEUROSCI.3293-04.2005.
In rats, naturally occurring variations in maternal care contribute to the development of individual differences in the behavioral and neuroendocrine responses to stress during adulthood. The dopamine (DA) projection to the medial prefrontal cortex (mPFC) plays an important role in mediating stress responsivity and is thought to be involved also in regulating sensorimotor gating. In the present study, we compared prepulse inhibition (PPI) of acoustic startle as well as the left and right mPFC DA stress responses in the adult offspring of high- and low-licking/grooming (LG) dams. Our data indicate that the offspring of low-LG animals are impaired on measures of PPI compared with high-LG animals. We also observed in low-LG animals a significant blunting of the mPFC DA stress responses that was lateralized to the right hemisphere, whereas in high-LG animals, the left and right mPFC DA stress responses were equally attenuated. Although mPFC levels of DA transporter did not differ between the two groups of animals, mPFC levels of catechol-O-methyl transferase immunoreactivity of low-LG animals were significantly lower than those of high-LG animals. These data provide evidence that variations in maternal care can lead to lasting changes in mPFC DA responsivity to stress and suggest the possibility that such changes in mesocorticolimbic DA function can also lead to deficits in sensorimotor gating.
在大鼠中,母性行为的自然变异会导致成年期对应激的行为和神经内分泌反应出现个体差异。多巴胺(DA)向内侧前额叶皮质(mPFC)的投射在介导应激反应性方面起重要作用,并且被认为也参与调节感觉运动门控。在本研究中,我们比较了高舔舐/梳理(LG)和低舔舐/梳理母鼠成年后代的听觉惊吓前脉冲抑制(PPI)以及左右mPFC的DA应激反应。我们的数据表明,与高LG动物相比,低LG动物的后代在PPI测量中受损。我们还观察到,低LG动物中mPFC的DA应激反应明显减弱,且这种减弱偏向于右半球,而在高LG动物中,左右mPFC的DA应激反应同等程度地减弱。尽管两组动物之间DA转运体的mPFC水平没有差异,但低LG动物的儿茶酚-O-甲基转移酶免疫反应性的mPFC水平显著低于高LG动物。这些数据证明,母性行为的变异可导致mPFC对压力的DA反应性产生持久变化,并提示中脑皮质边缘DA功能的此类变化也可能导致感觉运动门控缺陷的可能性。