Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Department of Psychology, Concordia University, 7141 Sherbrooke Street West SP 244, Montreal, QC, H4B-1R6, Canada.
Psychopharmacology (Berl). 2014 Feb;231(4):753-64. doi: 10.1007/s00213-013-3292-5. Epub 2013 Oct 6.
Drug-associated environmental stimuli elicit craving in humans and drug-seeking in animals.
We tested the hypothesis that Pavlovian-conditioned alcohol-seeking is mediated by dopamine, using rats from two vendors.
Male, Long-Evans rats (220-240 g) from Charles River (St-Constant, QC, Canada) and Harlan Laboratories (Indianapolis, IN, USA) received 21 sessions of intermittent, 24-h access to ethanol (15 %, v/v) and water in the home-cage. Subsequently, rats were trained to discriminate between one conditioned stimulus (CS+) that was paired with ethanol (0.2 ml per CS+) and a second stimulus (CS-) that was not. Entries into a fluid port where ethanol was delivered were recorded. Next, rats were exposed to a different context where cues and ethanol were withheld. At test, responding to the CS+ and CS- without ethanol was assessed in the second, non-alcohol context. Injections (1 ml/kg; s.c.) of the dopamine D1-receptor antagonist SCH 23390 (0, 3.33, and 10 μg/kg) or dopamine D2-receptor antagonist eticlopride (0, 5, and 10 μg/kg) were administered before test.
Home-cage alcohol consumption was higher in Harlan rats than Charles River rats. At test, saline-treated rats responded more to the alcohol-predictive CS+ than the CS-. While SCH 23390 attenuated CS+ responding in rats from both vendors, eticlopride reduced CS+ responding in Harlan rats only. Subsequently, SCH 23390 but not eticlopride attenuated CS+ responding when the CS+ was again paired with ethanol.
These results indicate important differences in alcohol consumption in Long-Evans rats from different suppliers, and highlight a novel role for dopamine in Pavlovian-conditioned alcohol-seeking.
药物相关的环境刺激会在人类中引起渴望，在动物中引起觅药行为。
我们使用来自两个供应商的大鼠检验了条件性酒精觅药由多巴胺介导的假说。
220-240 克的雄性长耳大仓鼠（来自 Charles River，加拿大圣康坦）和 Harlan 实验室（美国印第安纳波利斯）接受了 21 次间歇性 24 小时的酒精（15%，v/v）和水的家庭笼内访问。随后，大鼠被训练区分一个与酒精（每 CS+0.2 毫升）配对的条件刺激（CS+）和一个不配对的第二刺激（CS-）。记录进入提供乙醇的液体端口的次数。接下来，大鼠被暴露在一个没有线索和乙醇的不同环境中。在测试中，在第二个非酒精环境中评估对 CS+和 CS-没有乙醇时的反应。在测试前，给予多巴胺 D1 受体拮抗剂 SCH 23390（0、3.33 和 10μg/kg）或多巴胺 D2 受体拮抗剂 eticlopride（0、5 和 10μg/kg）的注射（1ml/kg；皮下）。
Harlan 大鼠的家庭笼内酒精消耗量高于 Charles River 大鼠。在测试中，盐水处理的大鼠对预测酒精的 CS+的反应比对 CS-的反应更多。虽然 SCH 23390 减弱了来自两个供应商的大鼠对 CS+的反应，但 eticlopride 仅降低了 Harlan 大鼠对 CS+的反应。随后，SCH 23390 但不是 eticlopride 减弱了 CS+再次与乙醇配对时的反应。
这些结果表明，来自不同供应商的长耳大仓鼠在酒精消耗方面存在重要差异，并强调了多巴胺在条件性酒精觅药中的新作用。
