Punishment and reinforcement by opioid receptor agonists in a choice procedure in rats.
Punishment and reinforcement by opioid receptor agonists in a choice procedure in rats.
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在大鼠的选择过程中阿片受体激动剂的惩罚和强化。
DOI：
10.1097/fbp.0000000000000436
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发表时间：
2019
影响因子：
1.6
通讯作者：
France,CharlesP
中科院分区：
文献类型：
--
作者：
Minervini,Vanessa;Osteicoechea,DanielaC;Casalez,Angelo;France,CharlesP
静脉注射（iv）药物自我管理仍然是评估药物滥用潜力的“黄金标准”。一种药物不能维持自我给药可能仅仅表明缺乏积极的强化作用，但也可能表明存在厌恶作用。对厌恶效应的敏感性被认为会影响药物使用的开始和维持以及复发。选择程序用于研究药物的积极强化作用，并在较小程度上研究药物的惩罚作用。实验1在大鼠中比较了μ-阿片受体激动剂瑞芬太尼（0.001-0.01 mg/kg/输注）、κ-阿片受体激动剂螺吲哚啉（0.0056-0.056 mg/kg/输注）和组胺（1.0 mg/kg/输注）在仅食物颗粒和静脉输注+食物颗粒之间的选择。为了测试一种惩罚性药物的历史是否会影响第二种药物的惩罚效果，实验2比较了有和没有组胺惩罚历史的大鼠对螺吲哚啉的敏感性。当组胺+颗粒剂是替代方案时，所有大鼠主要选择单独颗粒剂，并且它们主要选择瑞芬太尼+颗粒剂而不是单独颗粒剂。在实验2中，螺旋胆碱对有组胺惩罚史的大鼠具有惩罚作用，但对未用药的大鼠则没有。这种食物选择程序对同一受试者中不同药物的强化和惩罚效应敏感，这表明该程序非常适合研究药物混合物（例如μ和κ激动剂）以及不同生理条件（例如疼痛）对强化和惩罚的影响。
Intravenous (iv) drug self-administration remains the ‘gold standard’for assessing abuse potential of drugs. Failure of a drug to maintain self-administration might indicate merely the absence of positive-reinforcing effects but might also indicate presence of aversive effects. Sensitivity to aversive effects is thought to affect the initiation and maintenance of drug use as well as relapse. Choice procedures are used to study positive-reinforcing effects of drugs and to a much lesser extent to study punishing effects of drugs. Experiment 1 compared the μ-opioid receptor agonist remifentanil (0.001–0.01 mg/kg/infusion), the κ-opioid receptor agonist spiradoline (0.0056–0.056 mg/kg/infusion), and histamine (1.0 mg/kg/infusion) in rats choosing between a food pellet only and an iv infusion+ a food pellet. To test whether a history with one punishing drug affects the punishing effects of a second drug, experiment 2 compared sensitivity with spiradoline in rats with and without a history of histamine punishment. All rats predominantly chose a pellet alone when histamine+ a pellet was the alternative, and they predominantly chose remifentanil+ a pellet over a pellet alone. In experiment 2, spiradoline was punishing in rats with a history of histamine punishment but not drug-naive rats. This food choice procedure is sensitive to reinforcing and punishing effects of different drugs in the same subjects, suggesting that the procedure is well-suited for studying drug mixtures (eg μ and κ agonists) and the impact of different physiological conditions (eg pain) on reinforcement and punishment.