Dobrovitsky Veronica, West Mark O, Horvitz Jon C
The Graduate Center, Program in Behavioral and Cognitive Neuroscience, City University of New York, New York, NY, USA.
Department of Psychology, CCNY, New York, NY, USA.
Eur J Neurosci. 2019 Nov;50(9):3403-3415. doi: 10.1111/ejn.14523. Epub 2019 Aug 19.
Nucleus accumbens dopamine plays a key role in reward-directed approach. Past findings suggest that dopamine's role in the expression of learned behavior diminishes with extended training. However, little is known about the central substrates that mediate the shift to dopamine-independent reward approach. In the present study, rats approached and inserted the head into a reward compartment in response to a cue signaling food delivery. On days 4 and 5 of 28-trial-per-day sessions, D1 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) infused to the NAc core reduced the probability and speed of cued approach. The disruptive effect of D1 receptor blockade was specific to the nucleus accumbens core and not seen with drug infusions to nearby dopamine target regions. In rats that received drug infusions after extended training (days 10 or 11), accumbens core D1 receptor blockade produced little effect on the expression of the same behavior. These results could have been due to a continued accumbens mediation of cued approach even after the behavior had become independent of accumbens D1 receptors. However, accumbens core ionotropic glutamate receptor blockade disrupted cued approach during early but not late stages of training, similar to the effects of D1 antagonist infusions. The results suggest that with extended training, a nucleus accumbens D1-dependent behavior becomes less dependent not only on nucleus accumbens D1 transmission but also on excitatory transmission in the nucleus accumbens. These findings fill an important gap in a growing literature on reorganization of striatal function over the course of training.
伏隔核多巴胺在奖赏导向性行为中起关键作用。以往研究结果表明，随着训练时间延长，多巴胺在习得行为表达中的作用会减弱。然而，对于介导向多巴胺非依赖性奖赏导向行为转变的中枢底物，我们知之甚少。在本研究中，大鼠在提示食物投递的线索出现时，会接近并将头部伸进奖赏隔室。在每天进行28次试验的第4天和第5天，向伏隔核核心注入D1受体拮抗剂R(+)-7-氯-8-羟基-3-甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓盐酸盐（SCH23390），会降低线索引导接近行为的概率和速度。D1受体阻断的破坏作用具有伏隔核核心特异性，向附近多巴胺靶区域注射药物时未观察到这种作用。在经过长时间训练（第10天或11天）后接受药物注射的大鼠中，伏隔核核心D1受体阻断对相同行为的表达几乎没有影响。这些结果可能是由于即使行为已变得不依赖伏隔核D1受体，伏隔核仍持续介导线索引导的接近行为。然而，伏隔核核心离子型谷氨酸受体阻断在训练早期而非晚期破坏了线索引导的接近行为，类似于D1拮抗剂注射的效果。结果表明，随着训练时间延长，一种依赖伏隔核D1的行为不仅对伏隔核D1传递的依赖性降低，而且对伏隔核中的兴奋性传递的依赖性也降低。这些发现填补了关于训练过程中纹状体功能重组的不断增长的文献中的一个重要空白。
