Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alta., Canada.
Dev Neurosci. 2011;33(2):85-98. doi: 10.1159/000324744. Epub 2011 May 12.
The present study investigated the effect of prenatal stress (PS) on juvenile behavior and adult amphetamine (AMPH) sensitization, as well as the effect of the interaction between experience (i.e. PS) and drug (i.e. AMPH) on cortical thickness and neuronal morphology in corticolimbic regions in rats. Juvenile male and female rats, exposed to gestational stress, were tested in behavioral tasks that included open field locomotion, elevated plus maze, novel object recognition, and play fighting behavior. The development and persistence of drug-induced behavioral sensitization in adults were tested by chronic AMPH administration and challenge, respectively. Spine density in corticolimbic regions was examined for structural plasticity. The findings showed that PS produced anxiety-like behavior in males. Furthermore, PS in males resulted in female-like play and enhanced partial rotation defense, whereas in females PS increased the probability of evasion in response to an attack. AMPH administration resulted in gradual increase in behavioral sensitization that persisted at least for 2 weeks; however, PS did not influence AMPH-induced behavioral sensitization in either male or female rats. Moreover, PS increased the spine density in the nucleus accumbens (NAc) and decreased it in the medial prefrontal cortex (mPFC) without any alteration in the orbital frontal cortex (OFC). Similarly, AMPH administration increased spine density in the NAc and mPFC, whereas a decrease was observed in the OFC. However, PS prevented the drug-induced alterations in the spine density observed in controls. In sum, PS modulated juvenile behavior and altered brain morphology without influencing AMPH-induced behavioral sensitization substantially.
本研究旨在探讨产前应激（PS）对青少年行为和成年安非他命（AMPH）敏化的影响，以及经验（即 PS）和药物（即 AMPH）相互作用对皮质厚度和皮质边缘区域神经元形态的影响。将孕鼠暴露于 PS 中，雄性和雌性幼鼠接受行为测试，包括旷场运动、高架十字迷宫、新物体识别和玩耍格斗行为。通过慢性 AMPH 给药和挑战，测试成年后药物诱导的行为敏化的发展和持续。检查皮质边缘区域的棘密度以研究结构可塑性。研究结果表明，PS 导致雄性出现焦虑样行为。此外，PS 导致雄性表现出类似雌性的玩耍行为和增强的部分旋转防御，而在雌性中 PS 增加了对攻击的逃避反应的可能性。AMPH 给药导致行为敏化逐渐增加，至少持续 2 周；然而，PS 并未影响雄性或雌性大鼠的 AMPH 诱导的行为敏化。此外，PS 增加了伏隔核（NAc）的棘密度，而减少了内侧前额叶皮质（mPFC）的棘密度，而眶额皮质（OFC）没有任何变化。同样，AMPH 给药增加了 NAc 和 mPFC 的棘密度，而 OFC 则减少了。然而，PS 阻止了对照组中观察到的药物诱导的棘密度变化。总之，PS 调节了青少年的行为并改变了大脑形态，而对 AMPH 诱导的行为敏化没有显著影响。
