Laboratory of Neuroimaging, NIAAA, NIH, Department of Health and Human Services, Bethesda, MD, United States.
Physiol Behav. 2010 Dec 2;101(5):713-8. doi: 10.1016/j.physbeh.2010.08.011. Epub 2010 Aug 27.
Dopamine (DA) and the DA D2 receptor (D2R) are involved in the rewarding and conditioned responses to food and drug rewards. Osborne-Mendel (OM) rats are genetically prone and S5B/P rats are genetically resistant to obesity when fed a high-fat diet. We hypothesized that the differential sensitivity of these two rat strains to natural rewards may also be reflected in sensitivity to drugs of abuse. Therefore, we tested whether OM and S5B/P rats showed a differential preference to cocaine using conditioned place preference (CPP). To also evaluate whether there is specific involvement of the D2R in this differential conditioning sensitivity, we then tested whether the D2R agonist bromocriptine (BC) would differentially affect the effects of cocaine in the two strains.
OM and S5B/P rats were conditioned with cocaine (5 or 10mg/kg) in one chamber and saline in another for 8days. Rats were then tested for cocaine preference. The effects of BC (0.5, 1, 5, 10, 20mg/kg) on cocaine preference were then assessed in subsequent test sessions.
OM rats did not show a significant preference for the cocaine-paired chamber on test day. Only the S5B/P rats showed cocaine CPP. Later treatment with only the highest dose of BC resulted in reduced cocaine CPP in S5B/P rats when treated with 5mg/kg cocaine and in OM rats treated with 10mg/kg cocaine.
Our results indicated that obesity-resistant S5B rats showed greater cocaine CPP than the obesity-prone OM rats. These findings do not support a theory of common vulnerability for reinforcer preferences (food and cocaine). However, they show that BC reduced cocaine conditioning effects supporting at least a partial regulatory role of D2R in conditioned responses to drugs.
多巴胺（DA）和 DA D2 受体（D2R）参与食物和药物奖励的奖赏和条件反应。当喂食高脂肪饮食时，Osborne-Mendel（OM）大鼠具有遗传易感性，而 S5B/P 大鼠具有遗传抗性，不会肥胖。我们假设这两种大鼠品系对自然奖励的敏感性差异也可能反映在对滥用药物的敏感性上。因此，我们使用条件位置偏好（CPP）测试 OM 和 S5B/P 大鼠对可卡因是否表现出不同的偏好。为了评估 D2R 是否具体参与这种差异调节敏感性，我们随后测试了 D2R 激动剂溴隐亭（BC）是否会对两种品系的可卡因效应产生不同的影响。
OM 和 S5B/P 大鼠用可卡因（5 或 10mg/kg）在一个室中和生理盐水在另一个室中进行 8 天的条件训练。然后，对大鼠进行可卡因偏好测试。随后在后续测试中评估 BC（0.5、1、5、10、20mg/kg）对可卡因偏好的影响。
OM 大鼠在测试日没有表现出对可卡因配对室的显著偏好。只有 S5B/P 大鼠表现出可卡因 CPP。当用 5mg/kg 可卡因处理 S5B/P 大鼠，或用 10mg/kg 可卡因处理 OM 大鼠时，随后仅用最高剂量的 BC 处理会导致 S5B/P 大鼠的可卡因 CPP 减少。
我们的结果表明，肥胖抗性 S5B 大鼠比肥胖易感 OM 大鼠表现出更强的可卡因 CPP。这些发现不支持强化偏好（食物和可卡因）具有共同易感性的理论。然而，它们表明 BC 降低了可卡因调节作用，支持 D2R 在药物条件反应中至少具有部分调节作用。
