Kirschmann Erin K Z, Mauna Jocelyn C, Willis Cory M, Foster Rebecca L, Chipman Amanda M, Thiels Edda
Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Learn Mem. 2014 Oct 16;21(11):606-15. doi: 10.1101/lm.035113.114. Print 2014 Nov.
Conditioned stimuli (CS) can modulate reward-seeking behavior. This modulatory effect can be maladaptive and has been implicated in excessive reward seeking and relapse to drug addiction. We previously demonstrated that exposure to an appetitive CS causes an increase in the activation of extracellular signal-regulated kinase (ERK) and cyclic-AMP response-element binding protein (CREB) in the nucleus accumbens (NAc) of rats, and that CS-evoked ERK activation is critical for CS control over reward seeking. To elucidate the mechanism that mediates CS-driven ERK activation in the NAc, we selectively blocked NMDA glutamate or D1 dopamine receptors in the NAc. To determine whether CS-driven ERK and CREB activation are linked, we selectively blocked ERK signaling in the NAc. We found that both NMDA and D1 receptors are critical for CS-driven ERK signaling in the NAc, and that this recruitment of the ERK cascade is responsible for increased CREB activation in the presence of the CS. Our findings suggest that activation of the NMDAR-D1R/ERK/CREB signal transduction pathway plays a critical role in the control of reward-seeking behavior by reward-predictive cues.
条件刺激（CS）可调节奖赏寻求行为。这种调节作用可能是适应不良的，并与过度的奖赏寻求和药物成瘾复发有关。我们之前证明，暴露于奖赏性CS会导致大鼠伏隔核（NAc）中细胞外信号调节激酶（ERK）和环磷酸腺苷反应元件结合蛋白（CREB）的激活增加，并且CS诱发的ERK激活对于CS对奖赏寻求的控制至关重要。为了阐明介导NAc中CS驱动的ERK激活的机制，我们选择性地阻断了NAc中的NMDA谷氨酸受体或D1多巴胺受体。为了确定CS驱动的ERK和CREB激活是否相关联，我们选择性地阻断了NAc中的ERK信号传导。我们发现，NMDA和D1受体对于NAc中CS驱动的ERK信号传导都至关重要，并且在CS存在的情况下，ERK级联反应的这种募集导致CREB激活增加。我们的研究结果表明，NMDAR-D1R/ERK/CREB信号转导通路的激活在奖赏预测线索对奖赏寻求行为的控制中起关键作用。
