Drugs of Abuse, Gender Differences, and Protection by Sweets

描述(由候选人提供)：老鼠会抑制糖精溶液的摄入，这种溶液预示着滥用药物的被动或主动(即自我)给药。最初，人们认为滥用药物会产生一种条件性的味道厌恶，类似于厌恶剂氯化锂引起的厌恶。然而，最近的证据表明，滥用药物的抑制效应是由于预期获得更有效的药物奖励而导致的自然奖励(即糖精线索)的贬值。这种现象被称为奖励比较[18]，当被动地给可卡因注射时，雄性和雌性大鼠都会发生这种现象，并且不同性别的大鼠在糖精摄入量上存在很大的个体差异。与小抑制鼠或生理盐水对照组相比，大抑制鼠对糖精提示的回避程度更高。当在男性身上进行静脉注射自我给药测试时，更多地避免使用糖精提示与更多的可卡因自我给药高度相关[23]。有趣的是，在我们的手中，女性似乎比男性对可卡因诱导的CS摄入抑制更具抵抗力，在这种模式下，她们服用的药物更少。这一发现有些出乎意料，因为大量文献表明，雌性大鼠比雄性大鼠服用更多的药物，对药物无条件刺激(US)的更多偏好应该与更多而不是更少地避免价值较低的味觉线索有关。这种分离使我们假设，糖精线索的可用性(即使每天只有5分钟)足以减少可卡因的自我给药行为，而且，甜味的这些保护作用在雌性大鼠身上比在雄性大鼠中更大。具体目标1测试糖精线索的可用性是否有助于减少可卡因自身给药的获得和恢复，以及这种影响是否在雌性大鼠中更大。特殊目的2测试这种现象是否需要雌激素。最后，《特定目标3》测试伏隔神经多巴胺在雌性大鼠身上是否更敏感。伏隔胺追踪自然奖励和滥用药物之间的比较。如果我们的预测被证明是正确的，数据将表明，尽管对奖励的敏感性增加可能会使女性在缺乏替代自然奖励的情况下容易上瘾，但当有价值的自然奖励可用时，它也可能具有高度的保护性。

DESCRIPTION (provided by candidate): Rats will suppress intake of a saccharin solution that predicts either the passive or the active (i.e., self-) administration of a drug of abuse. Initially, it was believed that drugs of abuse were producing a conditioned taste aversion, similar to that induced by the aversive agent, lithium chloride. More recent evidence, however, suggests that the supressive effects of drugs of abuse are caused by devaluation of the natural reward (i.e., the saccharin cue) in anticipation of the availability of the more potent drug reward. This phenomenon, referred to reward comparison [18], occurs in both male and female rats when the cocaine is administered passively and large individual differences in saccharin intake are evident amongst rats of each sex. The large suppressing rats show greater avoidance of the saccharin cue than do either small suppressing rats or the saline controls. When tested using iv self-administration in males, greater avoidance of the saccharin cue is highly correlated with greater cocaine self-administration [23]. Interestly, in our hands, females appear to be more resistant to cocaine-induced suppression of CS intake than males and they take less drug in this paradigm. This finding was somewhat unexpected because a substantial amount of literature shows that female rats take more drug than male rats and greater preference for the drug unconditioned stimulus (US) should be associated with more, rather than less, avoidance of the less valuable taste cue. This disjunction led us to hypothesize that the availability of the saccharin cue (even for just 5 min/day) is sufficient to reduce cocaine self-administration behavior and, moreover, that these protective effects of the sweet are greater in female than in male rats. Specific Aim 1 tests whether the availability of the saccharin cue serves to reduce acquisition and reinstatement of cocaine selfadministration and whether this effect is greater in female rats. Specific Aim 2 tests whether estrogen is required for this phenomenon. Finally, Specific Aim 3 tests whether accumbens dopamine, which tracks the comparison between natural rewards and drugs of abuse, is more sensitive in the female rat. If our predictions prove correct, the data will suggest that, while increased sensitivity to reward may predispose females to addiction in the absence of alternative natural rewards, it also may be highly protective when a valued natural reward is available.