Jedynak Jakub P, Uslaner Jason M, Esteban José A, Robinson Terry E
Neuroscience Program, The University of Michigan, Ann Arbor, MI, USA.
Eur J Neurosci. 2007 Feb;25(3):847-53. doi: 10.1111/j.1460-9568.2007.05316.x.
Repeated exposure to psychostimulant drugs produces long-lasting changes in dendritic structure, presumably reflecting a reorganization in patterns of synaptic connectivity, in brain regions that mediate the psychomotor activating and incentive motivational effects of these drugs, including the nucleus accumbens and prefrontal cortex. However, repeated exposure to psychostimulant drugs also facilitates a transition in the control of some behaviors from action-outcome associations to behavior controlled by stimulus-response (S-R) habits. This latter effect is thought to be due to increasing engagement and control over behavior by the dorsolateral (but not dorsomedial) striatum. We hypothesized therefore that repeated exposure to methamphetamine would differentially alter the density of dendritic spines on medium spiny neurons (MSNs) in the dorsolateral vs. dorsomedial striatum. Rats were treated with repeated injections of methamphetamine, and 3 months later dendrites were visualized using Sindbis virus-mediated green fluorescent protein (GFP) expression in vivo. We report that prior exposure to methamphetamine produced a significant increase in mushroom and thin spines on MSNs in the dorsolateral striatum, but a significant decrease in mushroom spines in the dorsomedial striatum. This may be due to changes in the glutamatergic innervation of these two subregions of the dorsal striatum. Thus, we speculate that exposure to psychostimulant drugs may facilitate the development of S-R habits because this reorganizes patterns of synaptic connectivity in the dorsal striatum in a way that increases control over behavior by the dorsolateral striatum.
反复接触精神兴奋药物会使树突结构产生持久变化，这大概反映了突触连接模式的重组，发生在介导这些药物精神运动激活和激励动机效应的脑区，包括伏隔核和前额叶皮层。然而，反复接触精神兴奋药物也会促使某些行为的控制从动作-结果关联向由刺激-反应（S-R）习惯控制的行为转变。后一种效应被认为是由于背外侧（而非背内侧）纹状体对行为的参与和控制增加所致。因此，我们推测反复接触甲基苯丙胺会对背外侧与背内侧纹状体中中等棘状神经元（MSN）上树突棘的密度产生不同影响。给大鼠反复注射甲基苯丙胺，3个月后在体内利用辛德毕斯病毒介导的绿色荧光蛋白（GFP）表达使树突可视化。我们报告称，先前接触甲基苯丙胺会使背外侧纹状体中MSN上的蘑菇状和细棘显著增加，但背内侧纹状体中蘑菇状棘显著减少。这可能是由于背侧纹状体这两个亚区谷氨酸能神经支配的变化。因此，我们推测接触精神兴奋药物可能会促进S-R习惯的形成，因为这会以增加背外侧纹状体对行为控制的方式重组背侧纹状体中的突触连接模式。
