Neuropsychology Doctoral Program, The Graduate Center of the City University of New York, New York, NY 10016, USA.
Department of Psychology, Queens College, City University of New York, Flushing, NY 11367, USA.
Eur J Pharmacol. 2018 Jan 5;818:480-485. doi: 10.1016/j.ejphar.2017.11.029. Epub 2017 Nov 20.
Conditioned stimuli (CSs) exert motivational effects on both adaptive and pathological reward-related behaviors, including drug taking and seeking. We developed a paradigm that allows us to investigate the neuropharmacology by which previously neutral stimuli acquire the capacity to function as CSs and elicit (intravenous) cocaine conditioned approach and used this paradigm to test the role of NMDA receptor stimulation in the acquisition of cocaine conditioned approach. Rats were injected systemically with the NMDA receptor antagonist, MK-801, before the start of 4 consecutive conditioning sessions, each of which consisted of 20 randomly presented light/tone (CS) presentations paired with cocaine infusion contingent upon nose pokes. Rats later were subjected to a CS-only test. To test the role of NMDA receptor stimulation in the already established conditioned approach, rats were injected with MK-801 prior to the CS-only test that occurred after 18 CS-cocaine conditioning sessions. Blockade of NMDA receptors significantly impaired the acquisition of cocaine-conditioned approach as indicated by the emission of significantly fewer nose pokes and significantly longer latencies to nose poke during CS presentations. When MK-801 treatment was applied after the acquisition of conditioned approach responding it had no effect on these measures. These results suggest that NMDA receptor stimulation plays an important role in the acquisition of reward-related conditioned responses driven by intravenous cocaine-associated CSs.
条件刺激（CSs）对适应性和病理性与奖励相关的行为（包括药物摄取和觅药）都具有动机效应。我们开发了一种范式，使我们能够研究神经药理学，通过该神经药理学，先前的中性刺激获得了作为 CS 发挥作用的能力，并引起（静脉内）可卡因条件性趋近，我们使用该范式来测试 NMDA 受体刺激在可卡因条件性趋近获得中的作用。在连续 4 次条件训练开始之前，大鼠系统注射 NMDA 受体拮抗剂 MK-801，每次训练由 20 次随机呈现的光/音（CS）呈现组成，与可卡因输注相关联，需要进行鼻探。大鼠随后进行 CS 仅测试。为了测试 NMDA 受体刺激在已经建立的条件趋近中的作用，在进行第 18 次 CS-可卡因条件训练后，大鼠在 CS 仅测试前接受 MK-801 注射。NMDA 受体阻断显著损害了可卡因条件趋近的获得，表现为 CS 呈现期间鼻探的次数明显减少，潜伏期明显延长。当 MK-801 治疗应用于获得条件趋近反应后，它对这些措施没有影响。这些结果表明，NMDA 受体刺激在由静脉内可卡因相关 CS 驱动的奖励相关条件反应的获得中发挥重要作用。
