Drugs of Abuse, Gender Differences, and Protection by Sweets

描述（由候选人提供）： 大鼠将抑制糖精溶液的摄入，该糖精溶液预测被动或主动（即，自我）滥用药物的管理。最初，人们认为滥用药物会产生一种条件性味觉厌恶，类似于厌恶剂氯化锂所引起的味觉厌恶。然而，最近的证据表明，滥用药物的抑制作用是由自然回报的贬值造成的（即，糖精提示），以预期更有效的药物奖励的可用性。当被动给予可卡因时，雄性和雌性大鼠都会出现这种现象，称为奖励比较[18]，并且在每种性别的大鼠中，糖精摄入量存在明显的个体差异。大的抑制大鼠表现出更大的避免糖精线索比小抑制大鼠或盐水对照。当在男性中使用静脉自我给药进行测试时，更大程度地避免糖精提示与更大程度的可卡因自我给药高度相关[23]。有趣的是，在我们的手中，女性似乎更耐可卡因诱导的抑制CS摄入量比男性，他们采取更少的药物在这个范例。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，对药物非条件刺激（US）的更大偏好应该与更多而不是更少地避免不太有价值的味觉线索有关。这种分离使我们假设，糖精提示的可用性（即使只有5分钟/天）足以减少可卡因自我给药行为，而且，这些保护作用的甜是在雌性大鼠比雄性大鼠更大。具体目标1测试糖精提示的可用性是否有助于减少可卡因自我给药的获得和恢复，以及这种效果是否在雌性大鼠中更大。具体目标2测试是否需要雌激素这种现象。最后，具体目标3测试了多巴胺，它跟踪自然奖励和滥用药物之间的比较，是否在雌性大鼠中更敏感。如果我们的预测被证明是正确的，数据将表明，虽然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时，它也可能具有高度的保护作用。

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.