The PPARγ Agonist Pioglitazone Fails to Alter the Abuse Potential of Heroin, But Does Reduce Heroin Craving and Anxiety.
The PPARγ Agonist Pioglitazone Fails to Alter the Abuse Potential of Heroin, But Does Reduce Heroin Craving and Anxiety.
复制标题
PPARγ 激动剂吡格列酮无法改变海洛因的滥用潜力，但可以减少海洛因的渴望和焦虑。
DOI：
10.1080/02791072.2018.1508789
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发表时间：
2018
影响因子：
2.8
通讯作者：
Comer,SandraD
中科院分区：
文献类型：
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作者：
Jones,JermaineD;Bisaga,Adam;Metz,VerenaE;Manubay,JeanneM;Mogali,Shanthi;Ciccocioppo,Roberto;Madera,Gabriela;Doernberg,Molly;Comer,SandraD
过氧化物酶体增殖物激活γ受体（PPARγ）激动剂吡格列酮（PIO）可能通过其对神经胶质的作用，在临床前模型中显示可改变海洛因的作用。到目前为止，这些结果尚未在人类中进行评估。在为期三周的研究期间，海洛因依赖者被随机分配至活性药物（45 mg，n= 14）或安慰剂（0 mg，n= 16）PIO维持治疗组。在丁丙诺啡（8 mg）稳定后，参与者开始了为期两周的测试期。在第一到第四个测试日，参与者可以通过口头选择来自我管理药物或金钱。在第五天，积极的海洛因和金钱的管理和参与者可以工作，以获得海洛因或金钱使用一个渐进的比例选择程序。试验第6-10天与试验第1-5天相同，不同之处在于，在其中一个试验周期间，安慰剂在前四天可用，而在另一周期间海洛因可用。PIO未能改变海洛因的强化或积极的主观效应，但它确实减少了海洛因渴望和整体焦虑。虽然我们无法复制在临床前模型中发现的强大作用，但这些数据提供了值得进一步探索的药物作用的指示。
Possibly through its effects on glia, the peroxisome proliferator-activated gamma receptor (PPARγ) agonist pioglitazone (PIO) has been shown to alter the effects of heroin in preclinical models. Until now, these results have not been assessed in humans. Heroin-dependent participants were randomized to either active (45 mg,n= 14) or placebo (0 mg,n= 16) PIO maintenance for the duration of the three-week study. After stabilization on buprenorphine (8 mg), participants began a two-week testing period. On the first to fourth test days, participants could self-administer drug or money by making verbal choices for either option. On the fifth day, active heroin and money were administered and participants could work to receive heroin or money using a progressive ratio choice procedure. Test days 6–10 were identical to test days 1–5 with the exception that, during one of the test weeks, placebo was available on the first four days, and during the other week heroin was available. PIO failed to alter the reinforcing or positive subjective effects of heroin, but it did reduce heroin craving and overall anxiety. Although we were unable to replicate the robust effects found in preclinical models, these data provide an indication of drug effects that deserves further exploration.