Perseveration of craving: effects of stimuli conditioned to drugs of abuse versus conventional reinforcers differing in demand.
Perseveration of craving: effects of stimuli conditioned to drugs of abuse versus conventional reinforcers differing in demand.
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DOI：
10.1111/adb.12374
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发表时间：
2017-07
影响因子：
3.4
通讯作者：
Weiss F
中科院分区：
文献类型：
--
作者：
Martin-Fardon R;Weiss F
联想学习对于建立对因果关系的适当反应和对环境变化的有效行为调整至关重要。然而，习得的联想也会促进不适应行为，如暴露在与毒品相关的刺激下的成瘾者无法控制的寻药行为。在这里，我们试图识别行为特征，以区分由高度有效但非成瘾的常规增强剂条件下的环境刺激产生的奖赏寻求和由成瘾药物条件刺激引起的奖赏寻求。训练大鼠在脱水过程中将辨别性(即上下文)刺激(S+)与可卡因、乙醇、可口甜液或水的可用性联系起来。在消退后，重新暴露于这些刺激下的反应恢复效应在大小和持久度方面得到确立。最初，S+产生了很强的复原力，无论与常规还是毒品奖励有关。然而，经过反复测试，S+诱导的奖赏寻求在甜味溶液刺激下下降到灭绝水平，而在可卡因或乙醇刺激下持续存在。在被限制饮水以诱导动机约束的大鼠中，S+支持持之以恒的恢复，与可卡因条件下的S+产生的恢复相同。研究结果表明，由环境刺激和滥用药物之间的关联引导的行为的特征是持之以恒的、显然对灭绝具有高度抵抗力的奖励寻求，而由与常规奖励相关的刺激控制的行为在没有主要强化的情况下很快就会消失。然而，由与自然奖赏相关的刺激引发的奖赏寻求在生理剥夺状态下可以变得坚持不懈。可能，持之以恒的药物寻找涉及的机制与那些进化为促进缓解生理剥夺以确保生存的机制重叠。
Associative learning is essential for establishing appropriate responses to cause-effect relationships and effective behavioral adjustments to environmental changes. However, learned associations also promote maladaptive behavior such as uncontrollable drug seeking in addicts exposed to drug-associated stimuli. Here, we sought to identify behavioral characteristics that distinguish reward seeking produced by environmental stimuli conditioned to highly potent but non-addictive conventional reinforcers from reward seeking induced by stimuli conditioned to addictive drugs. Rats were trained to associate discriminative (i.e., contextual) stimuli (S+) with availability of cocaine, ethanol, palatable sweet solutions, or water during dehydration. Following extinction, response-reinstating effects of re-exposure to these stimuli were established in terms of magnitude and perseveration. Initially, the S+ produced strong reinstatement irrespective of association with conventional or drug reward. However, with repeated testing, S+-induced reward seeking decreased to extinction levels when motivated by the sweet solutions but perseverated when motivated by cocaine or ethanol. In rats placed on water restriction to induce a motivational constraint, the S+ supported perseverating reinstatement identical to that produced by an S+ conditioned to cocaine. The findings suggest that behavior guided by associations between environmental stimuli and drugs of abuse are characterized by perseverating, apparently highly extinction-resistant reward seeking, whereas behavior controlled by stimuli associated with conventional reward extinguishes rapidly in the absence of primary reinforcement. Reward seeking elicited by stimuli associated with natural reward can, however, become perseverative during physiological deprivation states. Possibly, perseverating drug seeking engages mechanisms overlapping with those that have evolved to promote alleviation of physiological deprivation to secure survival.