Self-administration of cocaine and remifentanil by monkeys: choice between single drugs and mixtures.
Self-administration of cocaine and remifentanil by monkeys: choice between single drugs and mixtures.
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DOI：
10.1007/s00213-010-2131-1
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发表时间：
2011-05
影响因子：
3.4
通讯作者：
Woolverton, William L.
中科院分区：
文献类型：
--
作者：
Freeman, Kevin B.;Woolverton, William L.
可卡因和阿片类药物经常被共同滥用。然而，到目前为止，还没有明确的证据表明药物相互作用使混合物成为更有效的强化剂。本研究在给猴子选择可卡因阿片类药物混合物和单一成分药物时，检测了可卡因阿片类药物组合的相对强化效力和最大有效性。让恒河猴选择注射可卡因（100 μg/kg/inj）和其他剂量的可卡因（10-560 μg/kg/inj）或瑞芬太尼（0.03-3.0 μg/kg/inj）。采用剂量加量模型选择可卡因和瑞芬太尼混合后的剂量组合，在加量的情况下，其强化效果相当于100 μg/kg/注射可卡因。然后让猴子选择(a)可卡因和预计相当于100 μg/kg/注射可卡因的混合物，(b)增加混合物和单一成分药物的剂量，以及(c)可卡因或瑞芬太尼的剂量在最高安全范围内。一般来说，猴子更喜欢超过100 μg/kg/注射的可卡因混合物，这是超加和性的证据。然而，当提供相对高剂量的单一成分药物作为替代品时，对混合物的偏好就停止了。当混合物中的剂量增加，并提供相对较高剂量的单一药物时，没有明显的偏好。所有的猴子都选择了最高剂量的瑞芬太尼而不是最高剂量的可卡因。目前的结果表明，可卡因-阿片类药物组合在效力方面可能是超级添加剂，但在最大限度上并不比单一成分药物更有效。
Cocaine and opioids are often co-abused. As yet, however, there is no clear evidence that the drugs interact to make the mixture a more effective reinforcer. The present study examined the relative reinforcing potency and maximum effectiveness of the cocaine–opioid combination in monkeys given a choice between cocaine–opioid mixtures and the single-component drugs. Rhesus monkeys were allowed to choose between injections of cocaine (100 μg/kg/inj) and other doses of cocaine (10–560 μg/kg/inj) or remifentanil (0.03–3.0 μg/kg/inj). A dose-addition model was used to select dose combinations for mixtures of cocaine and remifentanil predicted to be equivalent to 100 μg/kg/inj of cocaine in reinforcing effect if the drugs were additive. The monkeys were then allowed to choose between (a) cocaine and mixtures predicted to be equivalent to 100 μg/kg/inj of cocaine, (b) increasing doses of the mixtures and the single-component drugs, and (c) cocaine or remifentanil at doses that were in the highest safe range. Generally, monkeys preferred the mixtures over 100 μg/kg/inj of cocaine, evidence for superadditivity. However, preferences for the mixture ceased when relatively high doses of single-component drugs were offered as alternatives. When doses within the mixture were raised and offered with relatively high doses of the single drugs, there was no clear preference for either option. The highest dose of remifentanil was chosen over the highest dose of cocaine by all monkeys. The current results indicate that cocaine–opioid combinations can be super-additive in terms of potency, but are not, at maximum, more effective than the single-component drugs.
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影响因子：
6
作者：
Coffin, PO;Galea, S;Tardiff, K
通讯作者：
Tardiff, K
DOI：
10.1124/jpet.104.076646
发表时间：
2005-03-01
影响因子：
3.5
作者：
Rowlett, JK;Rodefer, JS;Spealman, RD
通讯作者：
Spealman, RD
影响因子：
4.2
作者：
Comer, S. D.;Ashworth, J. B.;Walsh, S. L.
通讯作者：
Walsh, S. L.
影响因子：
2.3
作者：
Downey, KK;Helmus, TC;Schuster, CR
通讯作者：
Schuster, CR
影响因子：
4.2
作者：
BICKEL, WK;DEGRANDPRE, RJ;HIGGINS, ST
通讯作者：
HIGGINS, ST