Chronic food restriction in rats augments the central rewarding effect of cocaine and the δ1 opioid agonist, DPDPE, but not the δ2 agonist, deltorphin-II
Chronic food restriction in rats augments the central rewarding effect of cocaine and the δ1 opioid agonist, DPDPE, but not the δ2 agonist, deltorphin-II
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DOI：
10.1007/s002130000523
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发表时间：
2000-10-01
影响因子：
3.4
通讯作者：
de Vaca, SC
中科院分区：
文献类型：
--
作者：
Carr, KD;Kim, GY;de Vaca, SC
基本原理：慢性食物限制增强阿片类药物、精神兴奋剂和NMDA拮抗剂的自我给药和运动刺激作用。尚未确定这些效应在多大程度上可归因于药物药代动力学和生物利用度与介导受影响行为功能的神经元回路敏感性的变化。最近的研究指出，中央适应性的变化，只要奖励，运动和c-fos诱导效应的安非他明和MK-801，直接注射到侧脑室，是更大的食物限制比随意喂养的大鼠。c-fos在小脑延髓核（NAC）壳的表达增加，特别是表明，食物限制可能通过调节多巴胺（DA）突触功能，在这个领域增加药物奖励。目的：本研究的第一个目的是调查可卡因和δ（1）阿片激动剂DPDPE的奖赏效应是否会因食物限制而增强，这两种药物都能增加DA突触传递。第二个目的是确定δ（2）阿片受体激动剂deltorphin-II是否受到食物限制的增强效应的影响，deltorphin-II已被报道具有DA非依赖性奖励效应。研究方法：药物的奖赏效应是根据它们降低外侧下丘脑自我刺激（LHSS）阈值的能力来测量的。结果如下：在单独的实验中，可卡因（50，100和150杯，ICV）和DPDPE（10和25杯，ICV）产生更大的阈值降低的影响，在食物限制比随意喂养的大鼠。Deltorphin-II（5.0，10和25 μ g，ICV）对奖励阈值没有影响，无论喂养方案如何。结论：虽然报告DA-独立的deltorphin-II奖励效应似乎提供了一种手段来检验的假设，即DA传输是关键的调制变量在食物限制的主题，奖励效果的这种化合物不能证明在LHSS范式。然而，目前的研究结果证实并扩展了先前的研究结果，即食物限制受试者滥用药物的自我管理能力增强是由于药物奖励最终共同途径的敏感性增强。
Rationale: Chronic food restriction augments the self-administration and locomotor stimulating effects of opiates, psychostimulants and NMDA antagonists. The extent to which these effects can be attributed to changes in drug pharmacokinetics and bioavailability versus sensitivity of the neuronal circuits that mediate the affected behavioral functions, has not been established. Recent studies point to central adaptive changes insofar as rewarding, locomotor and c-fos-inducing effects of amphetamine and MK-801, injected directly into the lateral ventricle, are greater in food-restricted than ad libitum fed rats. The increased expression of c-fos in nucleus accumbens (NAC) shell, in particular, suggests that food restriction may augment drug reward by modulating dopamine (DA) synaptic function in this area. Objectives: The first purpose of this study was to investigate whether the rewarding effects of cocaine and the delta (1) opioid agonist DPDPE, both of which increase DA synaptic transmission, are augmented by food restriction. The second purpose was to determine whether the delta (2) opioid agonist, deltorphin-II, which has been reported to exert DA-independent rewarding effects, is subject to the potentiating effect of food restriction. Methods: Rewarding effects of drugs were measured in terms of their ability to lower the threshold for lateral hypothalamic self-stimulation (LHSS) using a rate-frequency method. Results: In separate experiments, cocaine (50, 100 and 150 mug, ICV) and DPDPE (10 and 25 mug, ICV) produced greater threshold-lowering effects in food-restricted than ad libitum fed rats. Deltorphin-II (5.0, 10 and 25 mug, ICV) had no effect on reward thresholds, regardless of feeding regimen. Conclusions: While the reported DA-independence of deltorphin-II rewarding effects seemed to offer a means of testing the hypothesis that DA transmission is the critical modulated variable in food-restricted subjects, rewarding effects of this compound could not be demonstrated in the LHSS paradigm. The present results do, however, confirm and extend prior findings indicating that the enhanced self-administration of abused drugs by food-restricted subjects is due to enhanced sensitivity of a final common pathway for drug reward.