Departamento de Bioquímica, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Department of Psychiatry and Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina.
Alcohol Clin Exp Res. 2018 Jun;42(6):1051-1061. doi: 10.1111/acer.13636. Epub 2018 Apr 30.
Conditioned stimuli (CS) that predict reward delivery acquire the ability to induce phasic dopamine release in the nucleus accumbens (NAc). This dopamine release may facilitate conditioned approach behavior, which often manifests as approach to the site of reward delivery (called "goal-tracking") or to the CS itself (called "sign-tracking"). Previous research has linked sign-tracking in particular to impulsivity and drug self-administration, and addictive drugs may promote the expression of sign-tracking. Ethanol (EtOH) acutely promotes phasic release of dopamine in the accumbens, but it is unknown whether an alcoholic reward alters dopamine release to a CS. We hypothesized that Pavlovian conditioning with an alcoholic reward would increase dopamine release triggered by the CS and subsequent sign-tracking behavior. Moreover, we predicted that chronic intermittent EtOH (CIE) exposure would promote sign-tracking while acute administration of naltrexone (NTX) would reduce it.
Rats received 14 doses of EtOH (3 to 5 g/kg, intragastric) or water followed by 6 days of Pavlovian conditioning training. Rewards were a chocolate solution with or without 10% (w/v) alcohol. We used fast-scan cyclic voltammetry to measure phasic dopamine release in the NAc core in response to the CS and the rewards. We also determined the effect of NTX (1 mg/kg, subcutaneous) on conditioned approach.
Both CIE and alcoholic reward, individually but not together, associated with greater dopamine to the CS than control conditions. However, this increase in dopamine release was not linked to greater sign-tracking, as both CIE and alcoholic reward shifted conditioned approach from sign-tracking behavior to goal-tracking behavior. However, they both also increased sensitivity to NTX, which reduced goal-tracking behavior.
While a history of EtOH exposure or alcoholic reward enhanced dopamine release to a CS, they did not promote sign-tracking under the current conditions. These findings are consistent with the interpretation that EtOH can stimulate conditioned approach, but indicate that the conditioned response may manifest as goal-tracking.
条件刺激（CS）可预测奖励的传递，从而获得在伏隔核（NAc）中诱导多巴胺相位释放的能力。这种多巴胺释放可能促进条件趋近行为，这种行为通常表现为趋近奖励传递部位（称为“目标追踪”）或 CS 本身（称为“标记追踪”）。先前的研究将标记追踪与冲动和药物自我给药特别联系起来，而且成瘾药物可能会促进标记追踪的表达。乙醇（EtOH）急性促进伏隔核中多巴胺的相位释放，但尚不清楚酒精奖励是否会改变 CS 引发的多巴胺释放。我们假设，用酒精奖励进行的条件反射训练会增加 CS 引发的多巴胺释放和随后的标记追踪行为。此外，我们预测慢性间歇性 EtOH（CIE）暴露会促进标记追踪，而纳曲酮（NTX）的急性给药会减少标记追踪。
大鼠接受 14 次 EtOH（3 至 5 g/kg，灌胃）或水，然后进行 6 天的条件反射训练。奖励是含有或不含 10%（w/v）酒精的巧克力溶液。我们使用快速扫描循环伏安法测量 NAc 核心中对 CS 和奖励的相位多巴胺释放。我们还确定了 NTX（1 mg/kg，皮下）对条件趋近的影响。
CIE 和酒精奖励单独但不共同作用，与对照条件相比，都会引起对 CS 的多巴胺释放增加。然而，这种多巴胺释放的增加与更大的标记追踪无关，因为 CIE 和酒精奖励都将条件性趋近从标记追踪行为转移到目标追踪行为。然而，它们都增加了对 NTX 的敏感性，从而减少了目标追踪行为。
虽然 EtOH 暴露或酒精奖励的历史增强了对 CS 的多巴胺释放，但在当前条件下，它们并没有促进标记追踪。这些发现与 EtOH 可以刺激条件性趋近的解释一致，但表明条件反应可能表现为目标追踪。
