Intramural Research program of the National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.
Intramural Research program of the National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.
Neuron. 2019 Jan 16;101(2):294-306.e3. doi: 10.1016/j.neuron.2018.11.025.
Addiction is a disorder of behavioral control and learning. While this may reflect pre-existing propensities, drug use also clearly contributes by causing changes in outcome processing in prefrontal and striatal regions. This altered processing is associated with behavioral deficits, including changes in learning. These areas provide critical input to midbrain dopamine neurons regarding expected outcomes, suggesting that effects on learning may result from changes in dopaminergic error signaling. Here, we show that dopamine neurons recorded in rats that had self-administered cocaine failed to suppress firing on omission of an expected reward and exhibited lower amplitude and imprecisely timed increases in firing to an unexpected reward. Learning also appeared to have less of an effect on reward-evoked and cue-evoked firing in the cocaine-experienced rats. Overall, the changes are consistent with reduced fidelity of input regarding the expected outcomes, such as their size, timing, and overall value, because of cocaine use.
成瘾是一种行为控制和学习障碍。虽然这可能反映了预先存在的倾向,但药物使用也通过引起前额叶和纹状体区域中结果处理的变化明显做出了贡献。这种改变的处理与行为缺陷有关,包括学习的变化。这些区域为中脑多巴胺神经元提供了关于预期结果的关键输入,这表明学习的影响可能来自多巴胺能错误信号的改变。在这里,我们表明,在自行给予可卡因的大鼠中记录的多巴胺神经元未能在预期奖励的缺失时抑制放电,并表现出对意外奖励的放电幅度降低且时间不准确的增加。在可卡因经验丰富的大鼠中,学习似乎对奖励诱发和线索诱发的放电也没有那么大的影响。总的来说,这些变化与输入关于预期结果的保真度降低有关,例如它们的大小、时间和整体价值,这是因为可卡因的使用。