Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
Neural Plast. 2012;2012:283829. doi: 10.1155/2012/283829. Epub 2012 Nov 1.
Adult-generated neurons in the dentate gyrus (DG) of the hippocampus play a role in various forms of learning and memory. However, adult born neurons in the DG, while still at an immature stage, exhibit unique electrophysiological properties and are also functionally implicated in learning and memory processes. We investigated the effects of extinction of drug-seeking behavior on the formation of immature neurons in the DG as assessed by quantification of doublecortin (DCX) immunoreactivity. Rats were allowed to self-administer heroin (0.03 mg/kg/infusion) for 12 days and then subjected either to 10 days of extinction training or forced abstinence. We also examined extinction responding patterns following heroin self-administration in glial fibrillary acidic protein thymidine kinase (GFAP-tk) transgenic mice, which have been previously demonstrated to show reduced formation of immature and mature neurons in the DG following treatment with ganciclovir (GCV). We found that extinction training increased DCX immunoreactivity in the dorsal DG as compared with animals undergoing forced abstinence, and that GCV-treated GFAP-tk mice displayed impaired extinction learning as compared to saline-treated mice. Our results suggest that extinction of drug-seeking behavior increases the formation of immature neurons in the DG and that these neurons may play a functional role in extinction learning.
海马齿状回（DG）中的成年神经元在各种形式的学习和记忆中发挥作用。然而，DG 中新生的神经元虽然仍处于不成熟阶段，但表现出独特的电生理特性，并且在学习和记忆过程中也具有功能意义。我们通过双皮质素（DCX）免疫反应性的定量评估，研究了药物寻求行为的消退对 DG 中未成熟神经元形成的影响。大鼠被允许自行注射海洛因（0.03mg/kg/次）12 天，然后进行 10 天的消退训练或强制戒断。我们还检查了在神经胶质纤维酸性蛋白胸苷激酶（GFAP-tk）转基因小鼠中进行海洛因自我给药后的消退反应模式，先前的研究表明，在用更昔洛韦（GCV）处理后，DG 中未成熟和成熟神经元的形成减少。我们发现，与强制戒断的动物相比，消退训练增加了 DG 背侧的 DCX 免疫反应性，并且与生理盐水处理的小鼠相比，GCV 处理的 GFAP-tk 小鼠显示出受损的消退学习能力。我们的结果表明，药物寻求行为的消退增加了 DG 中未成熟神经元的形成，并且这些神经元可能在消退学习中发挥功能作用。
