Mirtazapine and ketanserin alter preference for gambling-like schedules of reinforcement in rats.
Mirtazapine and ketanserin alter preference for gambling-like schedules of reinforcement in rats.
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DOI：
10.1016/j.pnpbp.2017.03.027
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发表时间：
2017-07-03
影响因子：
5.6
通讯作者：
Celeste T
中科院分区：
文献类型：
--
作者：
Persons AL;Tedford SE;Celeste T
药物成瘾和行为成瘾具有重叠的特征，例如，在成本/效益决策任务中，两者都表现出对更大但成本更高的强化选项的偏好。我们之前的工作表明，混合功能的血清素化合物米氮平可以减弱由滥用药物引起的老鼠的行为。为了将这项工作扩展到行为成瘾，我们在这里确定了米氮平和/或酮舍林（另一种混合功能的血清素作用化合物）是否可以改变大鼠的独立于药物（或食物）激励奖励的决策。因此，我们在大鼠中开发了一种新颖的可变比率任务，其中颅内自我刺激被用作正强化物。使用杠杆按压进行不同级别的大脑刺激，操作任务提供了在按固定比例计划（即可预测的奖励）传递的小脑刺激电流和按照不可预测数量的响应传递的大脑刺激电流（即可变比例计划）之间的选择。这项任务可以展示个体偏好并检测药物治疗期间动机影响的变化。一旦建立了基线偏好，我们就确定米氮平或酮色林预处理显着降低了对赌博式强化计划后出现的大强化物的偏好。第二天，当老鼠在没有药物的情况下进行测试时，对不可预测的大强化物选择的偏好又恢复了。这些数据表明，米氮平和酮色林可以减少对更大、更昂贵的强化方案的偏好，并说明这些药物改变行为的潜力。
Drug and behavioral addictions have overlapping features, e.g., both manifest preference for larger, albeit costlier, reinforcement options in cost/benefit decision-making tasks. Our prior work revealed that the mixed-function serotonergic compound, mirtazapine, attenuates behaviors by rats motivated by abused drugs. To extend this work to behavioral addictions, here we determined if mirtazapine and/or ketanserin, another mixed-function serotonin-acting compound, can alter decision-making in rats that is independent of drug (or food)-motivated reward. Accordingly, we developed a novel variable-ratio task in rats wherein intracranial self-stimulation was used as the positive reinforcer. Using lever pressing for various levels of brain stimulation, the operant task provided choices between a small brain stimulation current delivered on a fixed-ratio schedule (i.e., a predictable reward) and a large brain stimulation delivered following an unpredictable number of responses (i.e., a variable-ratio schedule). This task allowed for demonstration of individualized preference and detection of shifts in motivational influences during a pharmacological treatment. Once baseline preference was established, we determined that pretreatment with mirtazapine or ketanserin significantly decreased preference for the large reinforcer presented after gambling-like schedules of reinforcement. When the rats were tested the next day without drug, preference for the unpredictable large reinforcer option was restored. These data demonstrate that mirtazapine and ketanserin can reduce preference for larger, costlier reinforcement options, and illustrate the potential for these drugs to alter behavior.
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影响因子：
2.7
作者：
Bhatia, Kamal S.;Szabo, Steven T.;Fowler, J. Corey;Wetsel, William C.;Lee, Tong H.
通讯作者：
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Mirtazapine改变了在大鼠中寻求与提示相关的甲基苯丙胺。
影响因子：
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作者：
Graves, Steven M.;Napier, T. Celeste
通讯作者：
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影响因子：
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影响因子：
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作者：
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