Alcohol, Cocaine, and Brain Stimulation-Reward in C57BI6/J and DBA2/J Mice
Alcohol, Cocaine, and Brain Stimulation-Reward in C57BI6/J and DBA2/J Mice
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DOI：
10.1111/j.1530-0277.2009.01069.x
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发表时间：
2010-01-01
影响因子：
3.2
通讯作者：
Malanga, C. J.
中科院分区：
文献类型：
--
作者：
Fish, Eric W.;Riday, Thorfinn T.;Malanga, C. J.
背景：快乐和奖励是饮酒的关键特征，在动物研究中很难测量。颅内自我刺激（ICSS）是一种行为方法，用于研究药物直接对大脑奖赏基础神经回路的影响。这些实验有两个目标：首先，确定酒精对 C57B16/J（C57）和 DBA2/J（DBA）小鼠品系的 ICSS 反应的影响；其次，将这些效果与精神兴奋剂可卡因的效果进行比较。方法：在雄性 C57 小鼠的下丘脑外侧植入单极刺激电极，并使其习惯于旋转轮子，通过提供奖励性电刺激（即脑刺激奖励或 BSR）来强化。使用曲线位移法，在口服酒精（0.3、0.6、1.0、1.7 g/kg）或水之前和之后立即测定 BSR 阈值 (theta(0))。测量血液酒精浓度（BAC）以确定酒精代谢对BSR阈值的影响。分别给小鼠腹腔注射可卡因（1.0、3.0、10.0、30.0 mg/kg）或盐水。结果：在 C57 小鼠中，0.6 g/kg 浓度的酒精使 BSR 阈值降低约 20%。在 BAC 上升（高达 40 mg/dl）但不下降的阶段。当给予 DBA 小鼠时。酒精降低了整个剂量范围内的 BSR 阈值；最大降幅约为50%。可卡因降低了两种菌株的 BSR 阈值。然而，可卡因剂量反应曲线向左移动表明，可卡因在 DBA 小鼠中比在 C57 小鼠中更有效。对于酒精和可卡因，对 BSR 阈值的影响与对操作反应率的影响无关。结论：在 C57 和 DBA 小鼠中，BSR 阈值的降低反映了酒精增强大脑奖赏神经机制的能力。 DBA 小鼠对酒精和可卡因的奖赏增强作用更加敏感，这表明小鼠品系的大脑奖赏神经机制存在差异，可以通过 ICSS 技术进行测量。
Background: Pleasure and reward are critical features of alcohol drinking that are difficult to measure in animal studies. Intracranial self-stimulation (ICSS) is a behavioral method for studying the effects of drugs directly on the neural circuitry that underlies brain reward. These experiments had 2 objectives: first, to establish the effects of alcohol on ICSS responding in the C57B16/J(C57) and DBA2/J (DBA) mouse strains; and second, to compare these effects to those of the psychostimulant cocaine.Methods: Male C57 mice were implanted with unipolar stimulating electrodes in the lateral hypothalamus and conditioned to spin a wheel for reinforcement by the delivery of rewarding electrical stimulation (i.e., brain stimulation-reward or BSR). Using the curve-shift method, the BSR threshold (theta(0)) was determined immediately before and after oral gavage with alcohol (0.3, 0.6, 1.0, 1.7 g/kg) or water. Blood alcohol concentration (BAC) was measured to determine the influence of alcohol metabolism on BSR threshold. Separately, mice were administered cocaine (1.0, 3.0, 10.0, 30.0 mg/kg) or saline intraperitoneally.Results: In C57 mice, the 0.6 g/kg close of alcohol lowered BSR thresholds, by about 20%. during the rising (up to 40 mg/dl), but not falling, phase of BAC. When given to the DBA mice. alcohol lowered BSR thresholds over the entire dose range; the largest reduction was by about 50%. Cocaine lowered BSR thresholds in both strains. However, cocaine was more potent in DBA mice than in C57 mice as revealed by a leftward shift in the cocaine dose-response curve. For both alcohol and cocaine, effects on BSR threshold were dissociable from effects on operant response rates.Conclusions: In C57 and DBA mice, reductions in BSR threshold reflect the ability of alcohol to potentiate the neural mechansims of brain reward. The DBA mice are more sensitive to the reward-potentiating effects of both alcohol and cocaine, suggesting that there are mouse strain differences in the neural mechanisms of brain reward that can be measured with the ICSS technique.