Singer Bryan F, Tanabe Lauren M, Gorny Grazyna, Jake-Matthews Charmaine, Li Yilin, Kolb Bryan, Vezina Paul
Committee on Neurobiology, The University of Chicago, Chicago, Illinois 60637, USA.
Biol Psychiatry. 2009 May 15;65(10):835-40. doi: 10.1016/j.biopsych.2008.12.020. Epub 2009 Feb 5.
Systemic exposure to amphetamine (AMPH) leads to a number of long-lasting neuroadaptations including changes in dendritic morphology in rat forebrain. It remains unknown whether these changes relate to associative drug conditioning or to nonassociative drug sensitization, two forms of plasticity produced by systemic exposure to AMPH.
We compared the behavioral, neuronal, and morphologic consequences of exposing rats to intraperitoneal (IP) AMPH to those of exposure to AMPH applied to the ventral tegmental area (VTA), infusions that sensitize AMPH-induced locomotion and nucleus accumbens (NAcc) DA overflow but do not produce drug conditioning.
Both IP and VTA AMPH exposure sensitized locomotion and NAcc DA overflow, but only IP AMPH exposure produced conditioned locomotion. Importantly, whereas IP AMPH exposure increased spine density and dendritic length and branching in the NAcc, exposure to VTA AMPH produced the opposite effects. A similar differentiation of effects was observed in cortical areas.
Together these findings suggest that the morphological changes seen following IP AMPH exposure reflect associative drug conditioning rather than nonassociative drug sensitization. The decreases observed in the NAcc of VTA AMPH exposed rats may reflect the inability of these infusions to support conditioning.
全身暴露于苯丙胺（AMPH）会导致许多持久的神经适应性变化，包括大鼠前脑树突形态的改变。目前尚不清楚这些变化是与联合药物条件反射有关，还是与非联合药物敏感化有关，这是全身暴露于AMPH所产生的两种可塑性形式。
我们将腹腔注射（IP）AMPH的大鼠与腹侧被盖区（VTA）注射AMPH的大鼠在行为、神经元和形态学方面的后果进行了比较，后者能使AMPH诱导的运动和伏隔核（NAcc）多巴胺溢出敏感化，但不会产生药物条件反射。
IP和VTA注射AMPH均使运动和NAcc多巴胺溢出敏感化，但只有IP注射AMPH会产生条件性运动。重要的是，IP注射AMPH会增加NAcc中的棘突密度、树突长度和分支，而VTA注射AMPH则产生相反的效果。在皮质区域也观察到了类似的效应差异。
这些发现共同表明，IP注射AMPH后出现的形态学变化反映的是联合药物条件反射，而非非联合药物敏感化。在VTA注射AMPH的大鼠的NAcc中观察到的减少可能反映了这些注射无法支持条件反射。
