Stuber Garret D, Wightman R Mark, Carelli Regina M
Curriculum in Neurobiology, The University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Neuron. 2005 May 19;46(4):661-9. doi: 10.1016/j.neuron.2005.04.036.
While Pavlovian and operant conditioning influence drug-seeking behavior, the role of rapid dopamine signaling in modulating these processes is unknown. During self-administration of cocaine, two dopaminergic signals, measured with 100 ms resolution, occurred immediately before and after the lever press (termed pre- and post-response dopamine transients). Extinction of self-administration revealed that these two signals were functionally distinct. Pre-response transients, which could reflect the motivation to obtain the drug, did not decline during extinction. Remarkably, post-response dopamine transients attenuated as extinction progressed, suggesting that they encode the learned association between environmental cues and cocaine. A third type of dopamine transient, not time locked to overt stimuli, decreased in frequency during extinction and correlated with calculated cocaine concentrations. These results show that dopamine release transients involved in different aspects of cocaine self-administration are highly plastic--differentially governed by motivation, learned associations linked with environmental stimuli, and the pharmacological actions of cocaine.
虽然巴甫洛夫条件反射和操作性条件反射会影响药物寻求行为，但快速多巴胺信号在调节这些过程中的作用尚不清楚。在可卡因自我给药过程中，以100毫秒分辨率测量的两种多巴胺能信号在杠杆按压之前和之后立即出现（称为反应前和反应后多巴胺瞬变）。自我给药的消退表明这两种信号在功能上是不同的。反应前瞬变可能反映获取药物的动机，在消退过程中并未下降。值得注意的是，随着消退的进行，反应后多巴胺瞬变减弱，这表明它们编码了环境线索与可卡因之间的习得关联。第三种类型的多巴胺瞬变，与明显刺激没有时间锁定关系，在消退过程中频率降低，并且与计算出的可卡因浓度相关。这些结果表明，参与可卡因自我给药不同方面的多巴胺释放瞬变具有高度可塑性——分别受动机、与环境刺激相关的习得关联以及可卡因的药理作用的不同调控。
