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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Discriminative and affective stimulus effects of dihydropyridine calcium channel modulators: relationship to antialcohol effects.
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Discriminative and affective stimulus effects of dihydropyridine calcium channel modulators: relationship to antialcohol effects.

机译：二氢吡啶钙通道调节剂的鉴别和情感刺激作用：与抗酒精作用的关系。

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Voltage-operated calcium channels (VOCCs) have been implicated in alcoholism. Thus, dihydropyridine (DHP) VOCC antagonists, such as nimodipine, reduce ethanol (EtOH) intake and preference in a variety of animal models of alcoholism. Paradoxically, the DHP VOCC agonist BAY k 8644 also demonstrates antialcohol effects in such models. The antialcohol effects of BAY k 8644 are stereoselective [the "agonistic" (-)-enantiomer being more potent than the "antagonistic" (+)-enantiomer], and are not blocked by pretreatment with nimodipine. The present review summarizes studies on the effects of DHPs in drug discrimination (DD), conditioned taste aversion (CTA), and conditioned place preference (CPP) paradigms, and discusses the possibility that the apparent antialcohol effect of these compounds is related to their discriminative and/or affective stimulus effects. In rats trained to discriminate nimodipine from vehicle, (-)-BAY k 8644 completely generalizes to the nimodipine cue; whereas, in rats trained to discriminate (-)-BAY k 8644, nimodipine completely generalizes to, and is unable to block, the (-)-BAY k 8644 cue. The same stereoselectivity is obtained for BAY k 8644 in DD paradigms and models of alcoholism. The apparent similarity of these profiles of activity suggests that a common neurobiological mechanism underlies the discriminative stimulus and antialcohol effects of DHPs. It appears unlikely, however, that the antialcohol effects of DHPs are based on substitution for, or blockade of, the EtOH cue, as these compounds were not found to generalize to, or block, the EtOH cue. Comparison of the effects of DHPs in CTA and CPP paradigms suggests that the affective stimulus effects of these compounds are dissimilar, and that the mechanism underlying the latter effects is probably not related to the mechanism underlying the antialcohol effects of DHP VOCC modulators.
机译：电压操纵的钙离子通道（VOCC）与酒精中毒有关。因此，二氢吡啶（DHP）VOCC拮抗剂（例如尼莫地平）会降低乙醇（EtOH）的摄入量，并在多种酒精中毒动物模型中均表现出偏爱。矛盾的是，DHP VOCC激动剂BAY k 8644在这种模型中也显示出抗酒精作用。 BAY k 8644的抗酒精作用是立体选择性的（“激动”（-）对映异构体比“拮抗”（+）对映异构体有效），并且不会被尼莫地平预处理所阻断。本综述概述了DHPs在药物鉴别（DD），条件性味觉厌恶（CTA）和条件性位置偏爱（CPP）范式中的作用研究，并讨论了这些化合物的明显抗酒精作用与其判别性有关的可能性。和/或情感刺激效果。在接受过训练以将尼莫地平与媒介物区分开的大鼠中，（-）-BAY k 8644完全泛化为尼莫地平的指示。相反，在接受过训练以区分（-）-BAY k 8644的大鼠中，尼莫地平完全泛化并且不能阻止（-）-BAY k 8644提示。在DD范例和酒精中毒模型中，BAY k 8644获得了相同的立体选择性。这些活性谱的明显相似性表明，DHP的区别性刺激和抗酒精作用是一种常见的神经生物学机制。但是，DHP的抗酒精作用似乎不太可能基于对EtOH线索的替代或阻断，因为未发现这些化合物会泛化或阻断EtOH线索。比较DHP在CTA和CPP范式中的作用，表明这些化合物的情感刺激作用是不同的，后者作用的潜在机制可能与DHP VOCC调节剂的抗酒精作用的潜在机制无关。

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