Prazosin differentially affects extinction of cocaine conditioned place preference on the basis of dose and initial preference.
Prazosin differentially affects extinction of cocaine conditioned place preference on the basis of dose and initial preference.
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DOI：
10.1097/wnr.0b013e32835ad246
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发表时间：
2012-12-19
期刊：
影响因子：
1.7
通讯作者：
Lattal KM
中科院分区：
文献类型：
--
作者：
Bernardi RE;Lattal KM
最近的研究表明，α1-肾上腺素能受体阻滞剂损害啮齿动物恐惧条件反射范式的消退。然而，使用其他条件反射范式对α1-肾上腺素能受体在消退中的作用进行的研究，例如检查滥用药物的条件反射效应的研究，提供了不一致的结果。在这篇文章中，我们重新分析和扩展了先前报道的α1-肾上腺素能受体拮抗剂哌唑嗪对可卡因诱导的大鼠位置偏爱消退的影响，在最初的偏好测试中使用了中位数分割。这项新的再分析，包括进一步的消光测试，揭示了一个矛盾的剂量效应。试验后单次给予较低剂量的哌唑嗪（0.3 mg/kg IP）可损害在初始试验期间表现出低于中位偏好的大鼠的消退，但对在初始试验期间表现出高于中位偏好的大鼠的消退无影响。相比之下，试验后单次给予较高剂量的哌唑嗪（1.0 mg/kg IP）可增强初始试验期间表现出高于中位数偏好的大鼠的消退，但对初始试验期间表现出低于中位数偏好的大鼠的消退无影响。与其他关于恐惧和药物条件反射的研究一致，这些结果表明α1-肾上腺素能受体参与了消退记忆的形成，但也表明了基于哌唑嗪剂量和初始学习强度的潜在重要的消退差异效应。
Recent work has demonstrated that α1-adrenergic receptor blockade impairs extinction in fear conditioning paradigms in rodents. However, studies of the role of α1-adrenergic receptors in extinction using other conditioning paradigms, such as those examining the conditioned effects of drug of abuse, have provided inconsistent results. In this article, we reanalyze and extend previously-reported findings of the effect of prazosin, an α1-adrenergic receptor antagonist, on the extinction of a cocaine-induced condition place preference in rats, using a median split of performance during the initial test for preference. This new reanalysis, which includes further extinction testing, revealed a paradoxical dose effect. A single post-test administration of a lower dose of prazosin, 0.3 mg/kg IP, impaired extinction in rats that demonstrated a below-median preference during initial testing, but had no effect on extinction in rats that demonstrated an above-median preference during initial testing. In contrast, a single post-test administration of a higher dose of prazosin, 1.0 mg/kg IP, enhanced extinction in rats that demonstrated an above-median preference during initial testing, but had no effect on extinction in rats that demonstrated a below-median preference during initial testing. Consistent with other studies of fear and drug conditioning, these results suggest the involvement of the α1-adrenergic receptor in the formation of extinction memories, but also indicate a potentially important differential effect on extinction based on the dose of prazosin and the strength of the initial learning.