Fidler Tara L, Clews Tara W, Cunningham Christopher L
Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, Portland, Oregon 97239-3098, USA.
Alcohol Clin Exp Res. 2006 Mar;30(3):414-28. doi: 10.1111/j.1530-0277.2006.00046.x.
There is a scarcity of behavioral models that will reliably produce ethanol intakes in rodents at levels that induce or maintain dependence. The present experiments were designed to reestablish a model that uses passive intragastric (IG) infusion of ethanol to induce tolerance/dependence/withdrawal before allowing rats to self-infuse ethanol intragastrically.
Sprague-Dawley rats were surgically implanted with IG catheters and allowed to recover. During the passive infusion phase (3-6 days), rats in the experimental group were passively infused with 10% (v/v) ethanol (3.3-12.2 g/kg/d). Rats in the control group were not infused. During the self-infusion phase (5-6 days), all rats had access to 2 flavored solutions. Licks on 1 solution were paired with ethanol infusions (20%, v/v) whereas licks on the other solution were unpaired. Experiments differed in the specific passive infusion parameters and in the ethanol intake limit during self-infusion.
Rats in the experimental groups self-infused more ethanol per day (means of 4-7 g/kg/d) than did rats in the control group (means of 0-2.6 g/kg/d). Across all 3 studies, individual total daily intakes exceeded 5 g/kg on 35% of the self-infusion days in ethanol-preexposed rats compared with <1% of the self-infusion days in the control rats. Ethanol-exposed rats also infused a substantially higher percentage (42%) of their total ethanol intake in relatively large bouts (>1.5 g/kg) compared with control rats (<10%). The addition of a daily 6-hour ethanol-free period during the passive infusion phase (in Experiments 2 and 3) led to higher ethanol intakes than in Experiment 1. Results of a control experiment showed that differences between experimental and control groups in Experiments 1 to 3 were a result of ethanol experience and not a general effect of differential infusion experience.
Relatively short periods of passive IG infusion of ethanol induced levels of ethanol self-infusion in genetically heterogeneous rats that were comparable with drinking intakes previously reported in rats selectively bred for ethanol intake/preference. Although the induction of dependence/withdrawal may have played a role in this outcome, an alternative interpretation is that experimental rats self-infused more ethanol because passive exposure produced tolerance to aversive pharmacological effects that would otherwise limit intake of the paired flavor because of development of conditioned taste aversion. The current findings provide a strong basis for future work designed to identify parametric determinants of this form of self-administration, its sensitivity to genetic influences, and its neurobiological substrates.
缺乏能使啮齿动物可靠地摄入可诱导或维持依赖水平乙醇的行为模型。本实验旨在重建一种模型，该模型在允许大鼠通过胃内自我灌注乙醇之前，先采用被动胃内（IG）灌注乙醇来诱导耐受性/依赖性/戒断反应。
对斯普拉格 - 道利大鼠进行手术植入IG导管并使其恢复。在被动灌注阶段（3 - 6天），实验组大鼠被动灌注10%（v/v）乙醇（3.3 - 12.2 g/kg/天）。对照组大鼠不进行灌注。在自我灌注阶段（5 - 6天），所有大鼠均可获取两种加味溶液。对一种溶液的舔舐与乙醇灌注（20%，v/v）配对，而对另一种溶液的舔舐则不配对。实验在特定的被动灌注参数以及自我灌注期间的乙醇摄入量限制方面存在差异。
实验组大鼠每天自我灌注的乙醇量（平均4 - 7 g/kg/天）高于对照组大鼠（平均0 - 2.6 g/kg/天）。在所有3项研究中，乙醇预先暴露组大鼠在自我灌注日中有35%的个体每日总摄入量超过5 g/kg，而对照组大鼠在自我灌注日中的这一比例小于1%。与对照组大鼠（<10%）相比，乙醇暴露组大鼠在相对较大剂量（>1.5 g/kg）的灌注中，其总乙醇摄入量的比例也显著更高（42%）。在被动灌注阶段增加每日6小时的无乙醇期（实验2和3）导致乙醇摄入量高于实验1。一项对照实验的结果表明，实验1至3中实验组与对照组之间的差异是乙醇体验的结果，而非不同灌注体验的一般效应。
相对较短时间的被动IG灌注乙醇可诱导遗传异质性大鼠的乙醇自我灌注水平，这与先前报道的为乙醇摄入量/偏好而选择性培育的大鼠的饮酒摄入量相当。尽管依赖性/戒断反应的诱导可能在这一结果中起了作用，但另一种解释是，实验大鼠自我灌注更多乙醇是因为被动暴露产生了对厌恶药理效应的耐受性，如果没有这种耐受性，由于条件性味觉厌恶的发展，配对味道的摄入量会受到限制。目前的研究结果为未来旨在确定这种自我给药形式的参数决定因素、其对遗传影响的敏感性及其神经生物学基础的工作提供了坚实的基础。
