Singer Bryan F, Bubula Nancy, Li Dongdong, Przybycien-Szymanska Magdalena M, Bindokas Vytautas P, Vezina Paul
Committee on Neurobiology, The University of Chicago, Chicago, IL, USA.
Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL, USA.
Neuropsychopharmacology. 2016 Jul;41(8):2178-87. doi: 10.1038/npp.2016.39. Epub 2016 Mar 16.
Repeated exposure to amphetamine leads to both associative conditioning and nonassociative sensitization. Here we assessed the contribution of neuronal ensembles in the nucleus accumbens (NAcc) to these behaviors. Animals exposed to amphetamine IP or in the ventral tegmental area (VTA) showed a sensitized locomotor response when challenged with amphetamine weeks later. Both exposure routes also increased ΔFosB levels in the NAcc. Further characterization of these ΔFosB+ neurons, however, revealed that amphetamine had no effect on dendritic spine density or size, indicating that these neurons do not undergo changes in dendritic spine morphology that accompany the expression of nonassociative sensitization. Additional experiments determined how neurons in the NAcc contribute to the expression of associative conditioning. A discrimination learning procedure was used to expose rats to IP or VTA amphetamine either Paired or Unpaired with an open field. As expected, compared with Controls, Paired rats administered IP amphetamine subsequently showed a conditioned locomotor response when challenged with saline in the open field, an effect accompanied by an increase in c-Fos+ neurons in the medial NAcc. Further characterization of these c-Fos+ cells revealed that Paired rats showed an increase in the density of dendritic spines and the frequency of medium-sized spines in the NAcc. In contrast, Paired rats previously exposed to VTA amphetamine showed neither conditioned locomotion nor conditioned c-Fos+ expression. Together, these results suggest a role for c-Fos+ neurons in the medial NAcc and rapid changes in the morphology of their dendritic spines in the expression of conditioning evoked by amphetamine-paired contextual stimuli.
反复接触苯丙胺会导致联合性条件反射和非联合性敏感化。在此，我们评估了伏隔核（NAcc）中神经元集群对这些行为的作用。腹腔注射或在腹侧被盖区（VTA）注射苯丙胺的动物，在数周后再次受到苯丙胺刺激时，会表现出敏感化的运动反应。两种给药途径还会增加伏隔核中ΔFosB的水平。然而，对这些ΔFosB+神经元的进一步表征显示，苯丙胺对树突棘密度或大小没有影响，这表明这些神经元不会经历伴随非联合性敏感化表达的树突棘形态变化。额外的实验确定了伏隔核中的神经元如何对联合性条件反射的表达产生作用。采用辨别学习程序，让大鼠在与旷场配对或不配对的情况下腹腔注射或在VTA注射苯丙胺。正如预期的那样，与对照组相比，腹腔注射苯丙胺的配对大鼠随后在旷场中受到盐水刺激时表现出条件性运动反应，同时内侧伏隔核中c-Fos+神经元增加。对这些c-Fos+细胞的进一步表征显示，配对大鼠伏隔核中树突棘密度增加，中等大小树突棘的频率增加。相比之下，先前在VTA注射苯丙胺的配对大鼠既没有表现出条件性运动，也没有条件性c-Fos+表达。总之，这些结果表明内侧伏隔核中的c-Fos+神经元及其树突棘形态的快速变化在由苯丙胺配对的情境刺激诱发的条件反射表达中发挥作用。
