Université de Bordeaux, Institut des Maladies Neurodégénératives, France.
CNRS, Institut des Maladies Neurodégénératives, France.
Addict Biol. 2018 May;23(3):880-888. doi: 10.1111/adb.12536. Epub 2017 Jul 13.
Drug addiction is a harmful preference for drug use over and at the expense of other non-drug-related activities. We previously identified in the rat orbitofrontal cortex (OFC) a mechanism that influences individual preferences between cocaine use and an alternative action rewarded by a non-drug reward (i.e. sweet water). Here, we sought to test the generality of this mechanism to a different addictive drug, heroin. OFC neuronal activity was recorded while rats responded for heroin or the alternative non-drug reward separately or while they chose between the two. First, we found that heroin-rewarded and sweet water-rewarded actions were encoded by two non-overlapping OFC neuronal populations and that the relative size of the heroin population represented individual drug choices. Second, OFC neurons encoding the preferred action-which was the non-drug action in the large majority of individuals-progressively fired more than non-preferred action-coding neurons 1 second after the onset of choice trials and around 1 second before the preferred action was actually chosen, suggesting a pre-choice neuronal competition for action selection. Together with a previous study on cocaine choice, the present study on heroin choice reveals important commonalities in how OFC neurons encode individual drug choices and preferences across different classes of drugs. It also reveals some drug-specific differences in OFC encoding activity. Notably, the proportion of neurons that non-selectively encode both the drug and the non-drug reward was higher when the drug was heroin (present study) than when it was cocaine (previous study). We will discuss the potential functional significance of these commonalities and differences in OFC neuronal activity across different drugs for understanding drug choice.
药物成瘾是指过度且优先选择使用药物，而牺牲其他非药物相关活动的有害偏好。我们之前在大鼠眶额皮层（OFC）中发现了一种机制，该机制影响个体在可卡因使用和另一种由非药物奖励（即甜水）奖励的替代行为之间的偏好。在这里，我们试图测试该机制在不同成瘾性药物（海洛因）中的普遍性。当大鼠分别对海洛因或替代非药物奖励做出反应，或在两者之间做出选择时，记录 OFC 神经元的活动。首先，我们发现海洛因奖励和甜水奖励的行为由两个不重叠的 OFC 神经元群体编码，并且海洛因群体的相对大小代表个体的药物选择。其次，编码首选动作的 OFC 神经元 - 在绝大多数个体中是无药物动作 - 在选择试验开始后 1 秒内比非首选动作编码神经元更频繁地放电，并且在首选动作实际选择之前约 1 秒左右，这表明在选择之前神经元对动作选择存在竞争。结合之前关于可卡因选择的研究，本研究关于海洛因选择揭示了 OFC 神经元如何在不同类别的药物中对个体药物选择和偏好进行编码的重要共性。它还揭示了 OFC 编码活动在某些药物特异性方面的差异。值得注意的是，当药物是海洛因时（本研究），而非选择性地编码药物和非药物奖励的神经元比例高于可卡因（先前的研究）。我们将讨论 OFC 神经元活动在不同药物之间的这些共性和差异对理解药物选择的潜在功能意义。
