Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, L470, Portland, OR, 97239-3098, USA.
Department of Psychology, Linfield University, McMinnville, OR, 97128, USA.
Psychopharmacology (Berl). 2021 Jan;238(1):55-66. doi: 10.1007/s00213-020-05658-x. Epub 2020 Sep 26.
Opioid receptor antagonists reliably alter the expression or extinction of ethanol's conditioned motivational effects as indexed by the place conditioning procedure, suggesting endogenous opioids are normally involved. These studies examined how exogenous stimulation of opioid receptors alters ethanol's conditioned rewarding and aversive effects.
Drugs that either directly (morphine) or indirectly (ethanol) stimulate opioid receptors were tested for their effects on the expression and extinction of ethanol-induced conditioned place preference (CPP) and conditioned place aversion (CPA).
Male DBA/2J mice were exposed to unbiased ethanol (2 g/kg) conditioning procedures that produced either CPP (experiments 1-2) or CPA (experiments 3-4). Morphine (0, 2.5, 5, or 10 mg/kg) was injected before three post-conditioning tests in experiments 1 and 3, whereas ethanol (0, 1, 2, or 3 g/kg) was injected before tests in experiments 2 and 4. All groups received vehicle on test 4 to determine whether the drug pretreatments altered the course of extinction.
Morphine dose-dependently enhanced CPP expression (experiment 1), but ethanol dose-dependently reduced CPP expression (experiment 2). Test 4 showed no differences between drug-treated mice and mice given vehicle on all tests. Morphine had no effect on expression or extinction of ethanol-induced CPA (experiment 3). The highest ethanol dose (3 g/kg) interfered with CPA expression, but not extinction (experiment 4).
Pretreatment drug effects on ethanol CPP and CPA expression were most likely a byproduct of their activity altering effects rather than opioid-receptor mediated modulation of ethanol's conditioned motivational effects. Neither drug affected the course of extinction.
阿片受体拮抗剂可靠地改变了乙醇的条件性动机效应的表达或消退，这以位置条件反射程序为指标，表明内源性阿片类物质通常参与其中。这些研究检查了外源性刺激阿片受体如何改变乙醇的条件性奖励和厌恶效应。
测试直接（吗啡）或间接（乙醇）刺激阿片受体的药物对乙醇诱导的条件性位置偏好（CPP）和条件性位置厌恶（CPA）表达和消退的影响。
雄性 DBA/2J 小鼠暴露于无偏置乙醇（2 g/kg）条件反射程序中，该程序产生 CPP（实验 1-2）或 CPA（实验 3-4）。在实验 1 和 3 中，在三个条件反射测试前注射吗啡（0、2.5、5 或 10 mg/kg），而在实验 2 和 4 中，在测试前注射乙醇（0、1、2 或 3 g/kg）。所有组在测试 4 中接受载体，以确定药物预处理是否改变了消退的过程。
吗啡剂量依赖性地增强 CPP 表达（实验 1），但乙醇剂量依赖性地降低 CPP 表达（实验 2）。测试 4 显示，在所有测试中，药物处理的小鼠与给予载体的小鼠之间没有差异。吗啡对乙醇诱导的 CPA 的表达或消退没有影响（实验 3）。最高乙醇剂量（3 g/kg）干扰了 CPA 的表达，但不干扰消退（实验 4）。
预处理药物对乙醇 CPP 和 CPA 表达的影响很可能是其改变作用的副产品，而不是阿片受体介导的对乙醇条件性动机效应的调节。两种药物都不影响消退的过程。
