Drug effects on multiple and concurrent schedules of ethanol- and food-maintained behaviour: context-dependent selectivity.
Drug effects on multiple and concurrent schedules of ethanol- and food-maintained behaviour: context-dependent selectivity.
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药物对乙醇和食物维持行为的多个和并发时间表的影响：上下文相关的选择性。
DOI：
10.1111/bph.12707
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发表时间：
2014
影响因子：
7.3
通讯作者：
Lamb,RJ
中科院分区：
文献类型：
--
作者：
Ginsburg,BC;Lamb,RJ
背景和目的与替代药物相比，更有效或更有效地减少乙醇维持行为的药物被认为是选择性的，并且被认为是有前途的酒精中毒药物疗法。这样的结果通常是使用单独的组或多个时间表获得的，其中乙醇和替代品可以单独或顺序使用。最近，我们观察到，当在多个时间表下依次提供乙醇和食物时，氟伏沙明和伐尼克兰具有选择性；然而，当乙醇和食物同时存在时，这种选择性就消失了。实验方法我们通过比较在多个时间表和同时时间表下减少乙醇和食物维持反应所需的几种药物的剂量来检查这些发现的普遍性。确定了利眠宁、2,5-二甲氧基-4-碘苯丙胺 (DOI)、间氯苯基哌嗪 (mCPP)、吗啡、纳曲酮和 d-苯丙胺的效果。 关键结果 在多重方案下，乙醇维持反应降低的 ED50 值显着不同，并且低于每种药物维持食物反应降低（显示选择性）的 ED50 值除氯氮卓（等效）和纳曲酮（不影响反应）外的药物。然而，这种选择性在并发时间表下消失甚至反转，因此减少乙醇和食物维持反应的 ED50 值没有不同（或者，在 DOI 后，食物维持反应的 ED50 低于乙醇维持反应）。结论和含义结果与氟伏沙明和伐尼克兰给药后观察到的结果一致，并表明选择性是检测依赖性的。这些结果表明需要仔细解释选择性药物效应，特别是在乙醇或替代品是唯一可用的程序强化的情况下获得的结果。
Background and PurposeDrugs that more potently or effectively reduce ethanol‐maintained behaviour versus an alternative are considered selective and are considered promising pharmacotherapies for alcoholism. Such results are often obtained using separate groups or multiple schedules where ethanol and the alternative are available alone or sequentially. Recently, we observed that when ethanol and food were available sequentially under a multiple schedule, fluvoxamine and varenicline were selective; yet this selectivity disappeared when ethanol and food were concurrently available.Experimental ApproachWe examined the generality of these findings by comparing doses of several drugs required to decrease ethanol‐ and food‐maintained responding under a multiple schedule and under a concurrent schedule. Effects were determined for chlordiazepoxide, 2,5‐dimethoxy‐4‐iodoamphetamine (DOI), meta‐chlorophenylpiperazine (mCPP), morphine, naltrexone and d‐amphetamine.Key ResultsUnder the multiple schedule, ED50values for decreases in ethanol‐maintained responding were significantly different and lower than ED50s for decreases in food‐maintained responding (demonstrating selectivity) for each drug except for chlordiazepoxide (which was equipotent) and naltrexone (which did not affect responding). However, this selectivity vanished or even inverted under the concurrent schedule, such that ED50values for decreasing ethanol‐ and food‐maintained responding were not different (or, following DOI, the ED50for food‐maintained responding was lower than for ethanol‐maintained responding).Conclusions and ImplicationsResults are consistent with those seen following fluvoxamine and varenicline administration, and suggest that selectivity is assay‐dependent. These results indicate the need for careful interpretation of selective drug effects, especially when obtained in situations where ethanol or the alternative is the only programmed reinforcement available.
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DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Nemenoff,RA;Kwok,YC;Shulman,GI;Blackshear,PJ;Osathanondh,R;Avruch,J
通讯作者：
Avruch,J
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2.9
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CUATRECASAS, P;PARIKH, I
通讯作者：
PARIKH, I
影响因子：
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作者：
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VONHOLT, C
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DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Avruch,J;Nemenoff,RA;Blackshear,PJ;Pierce,MW;Osathanondh,R
通讯作者：
Osathanondh,R
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DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Roth,RA;Mesirow,ML;Cassell,DJ
通讯作者：
Cassell,DJ