Yohimbine increases opioid-seeking behavior in heroin-dependent, buprenorphine-maintained individuals.
Yohimbine increases opioid-seeking behavior in heroin-dependent, buprenorphine-maintained individuals.
复制标题
DOI：
10.1007/s00213-012-2868-9
复制
发表时间：
2013-02
影响因子：
3.4
通讯作者：
Steinmiller, Caren L.
中科院分区：
文献类型：
--
作者：
Greenwald, Mark K.;Lundahl, Leslie H.;Steinmiller, Caren L.
在实验动物中，生物应激物育亨宾（α2-去甲肾上腺素能自身受体拮抗剂）促进药物寻求。人类实验室研究表明，心理压力可以增加药物渴望，但压力不会改变药物寻求。这项临床研究测试育亨宾是否增加阿片类药物寻求行为。10名海洛因依赖、丁丙诺啡（8 mg/天）稳定的志愿者，采样两个剂量的氢吗啡酮（12和24 mg IM，以平衡顺序，标记为药物A [第1阶段]和药物B [第2阶段]）。在随后的六个阶段（受试者内，双盲，随机交叉设计）中，志愿者可以在12个试验选择的累进比例任务中做出反应，以获得不同口服育亨宾预处理剂量（0，16.2和32.4 mg）后的氢吗啡酮采样剂量（药物A或B）单位（1或2 mg）与金钱（2美元）。行为经济需求强度和峰值响应（Omax）显着高于氢吗啡酮2毫克比1毫克。与安慰剂相比，育亨宾显著增加了氢吗啡酮需求的不弹性，氢吗啡酮1 mg单位（安慰剂、育亨宾16.2和32.4 mg剂量的Pmax分别为909、3647和3225）比氢吗啡酮2 mg单位（Pmax分别为2656、3193和3615）更明显。育亨宾产生显著但临床上适度的剂量依赖性血压升高（收缩压<15 mmHg，舒张压<10 mmHg）和阿片类戒断症状，并减少阿片类激动剂症状和兴奋情绪。这些研究结果与临床前数据一致，表明育亨宾增加了药物寻求;在这项研究中，这些作用发生时没有临床显著的主观痛苦或渴望增加，部分依赖于阿片类药物单位剂量。
In laboratory animals, the biological stressor yohimbine (α2-noradrenergic autoreceptor antagonist) promotes drug seeking. Human laboratory studies have demonstrated that psychological stressors can increase drug craving but not that stressors alter drug seeking. This clinical study tested whether yohimbine increases opioid seeking behavior. Ten heroin-dependent, buprenorphine (8-mg/day) stabilized volunteers, sampled two doses of hydromorphone (12 and 24 mg IM in counterbalanced order, labeled Drug A [session 1] and Drug B [session 2]). During each of six later sessions (within-subject, double blind, randomized crossover design), volunteers could respond on a 12-trial choice progressive ratio task to earn units (1 or 2 mg) of the sampled hydromorphone dose (Drug A or B) vs. money ($2) following different oral yohimbine pretreatment doses (0, 16.2 and 32.4 mg). Behavioral economic demand intensity and peak responding (Omax) were significantly higher for hydromorphone 2-mg than 1-mg. Relative to placebo, yohimbine significantly increased hydromorphone demand inelasticity, more so for hydromorphone 1-mg units (Pmax = 909, 3647 and 3225 for placebo, 16.2 and 32.4 mg yohimbine doses, respectively) than hydromorphone 2-mg units (Pmax = 2656, 3193 and 3615, respectively). Yohimbine produced significant but clinically modest dose-dependent increases in blood pressure (systolic ≈15 and diastolic ≈10 mmHg) and opioid withdrawal symptoms, and decreased opioid agonist symptoms and elated mood. These findings concur with preclinical data by demonstrating that yohimbine increases drug seeking; in this study, these effects occurred without clinically significant subjective distress or elevated craving, and partly depended on opioid unit dose.
登录
查看更多内容
影响因子：
2.7
作者：
Feltenstein, Matthew W.;See, Ronald E.
通讯作者：
See, Ronald E.
DOI：
10.1007/bf02191958
发表时间：
1992-07-01
影响因子：
4.7
作者：
ALBUS, M;ZAHN, TP;BREIER, A
通讯作者：
BREIER, A
影响因子：
4.2
作者：
BICKEL, WK;DEGRANDPRE, RJ;HIGGINS, ST
通讯作者：
HIGGINS, ST
影响因子：
4.2
作者：
Greenwald, Mark K.
通讯作者：
Greenwald, Mark K.
影响因子：
2.7
作者：
Banna, Kelly M.;Back, Sudie E.;Do, Phong;See, Ronald E.
通讯作者：
See, Ronald E.