Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut des Maladies Neurodégénératives, Bordeaux, France.
Biol Psychiatry. 2013 Feb 1;73(3):271-9. doi: 10.1016/j.biopsych.2012.08.011. Epub 2012 Sep 15.
Recent neuroimaging studies have shown that people with cocaine addiction retain some degree of control over drug craving that correlates with neural activity in the lateral prefrontal cortex (PFC). Here, we report similar findings in a rat model of inhibitory control of cocaine seeking.
Rats actively responding for cocaine were trained to stop responding when presented with a discriminative stimulus that signaled lack of reinforcement. Rats were then tested for inhibitory control of cocaine seeking in novel behavioral contexts and in circumstances when cocaine seeking is particularly intense (e.g., following drug priming). The role of neuronal activity in different subregions of the PFC was assessed using local pharmacologic inactivation and c-Fos immunohistochemistry.
Rats progressively acquired the ability to stop cocaine seeking, even during drug intoxication and after a long history of cocaine self-administration. Inhibitory control of cocaine seeking was flexible, sufficiently strong to block cocaine-primed reinstatement, and selectively depended on increased neuronal activity within the prelimbic PFC, which is considered the rodent functional homolog of the human lateral PFC.
Parallel evidence in both animal models and humans indicate that recruitment of prefrontal inhibitory control of drug seeking is still functional after prolonged cocaine use. Preclinical investigation of the mechanisms underlying this capacity may contribute to designing new behavioral and/or pharmacologic strategies to promote its use for the prevention of relapse in addiction.
最近的神经影像学研究表明，可卡因成瘾者在一定程度上仍能控制对药物的渴望，这种控制与外侧前额叶皮层（PFC）的神经活动相关。在这里，我们在抑制可卡因寻求的大鼠模型中报告了类似的发现。
主动寻求可卡因的大鼠接受训练，当出现表示缺乏强化的辨别性刺激时停止反应。然后，在新的行为环境中和可卡因寻求特别强烈的情况下（例如，在药物引发后）测试大鼠对可卡因寻求的抑制控制。使用局部药理学失活和 c-Fos 免疫组织化学评估 PFC 不同子区域的神经元活动的作用。
大鼠逐渐获得了停止可卡因寻求的能力，即使在药物中毒和长期可卡因自我给药后也是如此。对可卡因寻求的抑制控制具有灵活性，足以阻止可卡因引发的复吸，并且选择性地依赖于前扣带皮层内神经元活动的增加，该区域被认为是人类外侧 PFC 的啮齿动物功能同源物。
动物模型和人类中的平行证据表明，在长期使用可卡因后，对药物寻求的前额叶抑制控制的招募仍然是功能性的。对这种能力的潜在机制的临床前研究可能有助于设计新的行为和/或药理学策略，以促进其在预防成瘾复发中的应用。
