Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA.
Neuropsychopharmacology. 2013 Jan;38(2):293-301. doi: 10.1038/npp.2012.168. Epub 2012 Sep 5.
Prenatal stress exposure (PSE) is known to increase addiction risk. Dopamine (DA) neurons in the ventral tegmental area (VTA) play an important role in addiction. In order to understand the cellular mechanisms underlying PSE-induced increase in addiction risk, we examined the effects of PSE on the electrical impulse activity of VTA DA neurons using the in vivo extracellular single-unit recording technique. Amphetamine self-administration was also conducted to confirm increased addiction risk after PSE. The PSE was carried out by restraining pregnant dams from GD 11 to 20. Adult male offspring (3-6 months old) were used in the experiments. Animals with PSE showed enhanced amphetamine self-administration compared with controls when amphetamine dose was reduced after acquisition. The number of spontaneously active VTA DA neurons was also reduced in PSE rats. The reduction was reversed by acute apomorphine that normally inhibits the impulse activity of DA neurons. The reversal effect suggests that PSE-induced reduction in the number of spontaneously active VTA DA neurons is caused by overexcitation to the extent of depolarization block. Furthermore, the reduced number of spontaneously active VTA DA neurons was also reversed by acute psychostimulants (eg, amphetamine; cocaine), which in control rats inhibited the activity of VTA DA neurons. The reversal effect on VTA DA neuron in PSE animals represents an actual increase in the impulse activity. This effect might contribute to increased responding to psychostimulants and mediate increased addiction risk after PSE.
产前应激暴露（Prenatal stress exposure，PSE）已知会增加成瘾风险。腹侧被盖区（Ventral tegmental area，VTA）中的多巴胺（Dopamine，DA）神经元在成瘾中起着重要作用。为了了解 PSE 引起的成瘾风险增加的细胞机制，我们使用体内细胞外单单元记录技术研究了 PSE 对 VTA DA 神经元电脉冲活动的影响。还进行了安非他命自我给药，以确认 PSE 后成瘾风险增加。PSE 是通过在 GD 11 至 20 期间限制怀孕的母鼠来进行的。成年雄性后代（3-6 个月大）用于实验。与对照组相比，PSE 动物在获得后减少安非他命剂量时表现出增强的安非他命自我给药。PSE 大鼠的 VTA DA 神经元自发性活动数量也减少。急性阿扑吗啡可逆转该减少，阿扑吗啡通常抑制 DA 神经元的冲动活动。这种逆转效应表明，PSE 诱导的 VTA DA 神经元自发性活动数量减少是由于过度兴奋导致去极化阻断。此外，急性精神兴奋剂（例如安非他命；可卡因）也可逆转 VTA DA 神经元的自发性活动数量减少，而在对照组大鼠中，这些精神兴奋剂抑制 VTA DA 神经元的活性。PSE 动物 VTA DA 神经元的这种逆转效应代表了冲动活动的实际增加。这种效应可能有助于增加对精神兴奋剂的反应，并介导 PSE 后成瘾风险的增加。
