Behavioral Methodology Facilitating Ethanol Reward

描述(由申请人提供)： 尽管乙醇(Etoh)使用的一个有益成分是毋庸置疑的，但它是 隔离和测试以下物质的积极强化效果不是一项简单的任务 乙醇对实验大鼠的影响。例如，静脉(IV)自我给药是 一种流行的行为方法来确定最受虐待的人的奖励成分 毒品，但不是艾托。事实上，关于IV Etoh的报道很少 自治和现有文件在范围上是有限的。在这样的研究中， 行为反应要求和乙醇摄入水平都非常高 低，这让人怀疑IV的表观动机特性 乙醇是集中调节的。然而，口服乙醇自我给药被广泛使用。 作为奖励乙醇效果的指标而被利用和接受。不幸的是， 即使利用基因选择的大鼠品系，也持续 在开始可靠的摄取之前，需要接触口服乙醇， 大概是为了适应令人厌恶的Etoh口味。然而，即使当 味觉因素被绕过(例如，肠外乙醇)，长时间接触 在观察到乙醇条件化奖励之前，仍然需要乙醇。之后 标准的条件反射程序，预先暴露于乙醇的大鼠展示 对乙醇配对环境的条件性位置偏好，但乙醇幼稚的大鼠 显示位置厌恶。这些发现表明了积极的强化作用。 乙醇预暴露后的乙醇中毒可能与乙醇诱导的神经适应性有关 改变而不是味觉习惯。本提案描述了一种 我们实验室制定的行为模型最终导致了高 自愿静脉注射和口服乙醇。在试点研究中，预先暴露于静脉注射的大鼠 通过自我给药乙醇/可卡因组合，证明是可靠的 仅对静脉注射乙醇有反应。自行静脉注射乙醇摄入量(0.5-2.0 G/kg/LHR)对应的血液酒精水平(BAL)约为。44-221 Mg/dL。这些BALS清楚地表明了乙醇和(在 高端)之前并未在自愿后得到经验证明 乙醇摄入量。此外，单独给药静脉注射乙醇的动物 随后喝了大约一杯。0.65g/kg无口服乙醇蔗糖褪色 会话。对IV Etoh自治的进一步分析将允许 无水乙醇疗效的神经生物学底物的鉴定 不受味觉因素的干扰。这项提案将调查 乙醇摄入量参数和时间进程的行为分析 和口服乙醇自我给药。体内微透析也将用于 乙醇诱导的动物伏隔核多巴胺水平升高的比较 自我注射无水乙醇和通过实验者接受无水乙醇- 行政管理。

DESCRIPTION (provided by applicant): Although a rewarding component of ethanol (ETOH) use cannot be disputed, it is not a trivial task to isolate and test the positive reinforcing effects of ETOH in laboratory rats. For example, intravenous (IV) self-administration is a popular behavioral method for determining reward constituents of most abused drugs, but not ETOH. Indeed, there are few reports of IV ETOH self-administration and existing papers are limited in scope. In such studies, behavioral response requirements and ETOH intake levels are both extremely low, bringing into question whether the apparent motivational properties of IV ETOH are centrally mediated. Oral ETOH self-administration, however, is widely utilized and accepted as an index of rewarding ETOH effects. Unfortunately, even with the utilization of genetically selected rat lines, sustained exposure to oral ETOH is required before reliable intake is initiated, presumably to allow for habituation to the aversive ETOH taste. Yet, even when taste factors are circumvented (e.g., parenteral ETOH), prolonged exposure to ETOH is still required before EtOH-conditioned reward can be observed. After standard conditioning procedures, rats pre-exposed to ETOH demonstrate conditioned place preferences to EtOH-paired environments, but ETOH-naive rats show place aversions. These findings suggest the positive reinforcing effects of ETOH following ETOH pre-exposure may be due to EtOH-induced neuroadaptive alterations rather than orosensory habituation. This proposal describes a behavioral model formulated in our laboratory that ultimately resulted in high voluntary IV and oral ETOH intake. In pilot studies, rats pre-exposed to IV ETOH by self-administering IV EtOH/cocaine combinations, demonstrated reliable responding to IV ETOH alone. Self-administered IV EtOH intake (0.5-2.0 g/kg/lhr) corresponded with blood alcohol levels (BAL) of approx. 44-221 mg/dL. These BALs clearly indicate pharmacological effects of ETOH and (at the high end) have not previously been empirically demonstrated after voluntary ETOH intake. In addition, animals that self- administered IV ETOH alone subsequently drank approx. 0.65 g/kg of ETOH without oral ETOH sucrose-fading sessions. Further analyses of IV ETOH self-administration will allow identification of neurobiological substrates of the rewarding aspects of ETOH without interference from orosensory factors. This proposal will investigate parameters of ETOH intake and time course through behavioral analyses of IV and oral ETOH self-administration. In vivo microdialysis will also be used to compare EtOH-induced increases in accumbens dopamine levels between animals self-administering IV ETOH and those receiving ETOH via experimenter- administration.