Biphasic reward effects are characteristic of both lorcaserin and drugs of abuse: implications for treatment of substance use disorders.
Biphasic reward effects are characteristic of both lorcaserin and drugs of abuse: implications for treatment of substance use disorders.
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DOI：
10.1097/fbp.0000000000000672
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发表时间：
2022-06-01
影响因子：
1.6
通讯作者：
De A
中科院分区：
文献类型：
--
作者：
Grasing KW;Burnell K;De A
Lorcaserin 是 2C 血清素受体 (5-HT2CR) 的适度选择性激动剂。尽管早期数据有希望，但它最近未能促进患者戒除可卡因，并被与多巴胺拮抗剂药物（抗精神病药）进行比较。在这里，我们回顾了这两类药物对药物强化的影响。除了不能有效治疗可卡因使用障碍外，多巴胺拮抗剂和氯卡色林都可以对多巴胺和奖赏行为产生双相作用。较低剂量会导致药物服用量增加，较高剂量会导致药物服用量减少。这种双相模式与某些兴奋剂、阿片类药物和镇静催眠药相同。以及没有滥用潜力的化合物，其中包括毒蕈碱和褪黑激素受体的激动剂。与吸毒减少相关的其他因素包括多巴胺拮抗剂的间歇给药和氯卡色林渐进比例给药方案的使用。氯卡色林的临床相关剂量远低于抑制可卡因强化行为的剂量，并且还可以在不同物种中强化相同的行为。药物强化行为的减弱仅发生在动物服用较高剂量后，不适合患者使用。总之，滥用药物和相关化合物通常充当奖赏行为的双相调节剂，特别是在广泛的剂量范围内进行评估时。这一特性可能反映了奖励系统的基本生理学，允许对行为产生稳态影响。
Lorcaserin is a modestly selective agonist for 2C serotonin receptors (5-HT2CR). Despite early promising data, it recently failed to facilitate cocaine abstinence in patients, and has been compared to dopamine antagonist medications (antipsychotics). Here, we review the effects of both classes on drug reinforcement. In addition to not being effective treatments for cocaine use disorder, both dopamine antagonists and lorcaserin can have biphasic effects on dopamine and reward behavior. Lower doses can cause enhanced drug taking with higher doses causing reductions. This biphasic pattern is shared with certain stimulants, opioids, and sedative-hypnotics; as well as compounds without abuse potential which include agonists for muscarinic and melatonin receptors. Additional factors associated with decreased drug taking include intermittent dosing for dopamine antagonists and use of progressive-ratio schedules for lorcaserin. Clinically relevant doses of lorcaserin were much lower than those that inhibited cocaine-reinforced behavior, and can also augment this same behavior in different species. Diminished drug-reinforced behavior only occurred in animals after higher doses which are not suitable for use in patients. In conclusion, drugs of abuse and related compounds often act as biphasic modifiers of reward behavior, especially when evaluated over a broad range of doses. This property may reflect the underlying physiology of the reward system, allowing homeostatic influences on behavior.