PHARMACOLOGICAL REGULATION OF INTRAVENOUS COCAINE AND HEROIN SELF-ADMINISTRATION IN RATS - A VARIABLE DOSE PARADIGM
PHARMACOLOGICAL REGULATION OF INTRAVENOUS COCAINE AND HEROIN SELF-ADMINISTRATION IN RATS - A VARIABLE DOSE PARADIGM
复制标题
DOI：
10.1016/0091-3057(89)90192-5
复制
发表时间：
1989-02-01
影响因子：
3.6
通讯作者：
WISE, RA
中科院分区：
文献类型：
--
作者：
GERBER, GJ;WISE, RA
老鼠被训练通过静脉自我注射单位剂量的可卡因或海洛因。每只大鼠每小时平均摄入量的一部分的恒定补充输注增加了连续输注之间的平均时间，但从小样本动物的数据来看，这种效果在统计学上并不可靠。开发了一种每次输注可变剂量（VAN）范例，该范例使得能够在单次测试期间测试几个单位剂量的可卡因或海洛因。以相同的频率但以不可预测的顺序向独立的大鼠组提供0.5、1.0和2.0 mg/kg可卡因或0.025、0.05和0.1 mg/kg海洛因的单位剂量。在每种情况下，连续输注之间的平均时间与前一次输注的对数剂量线性相关。匹莫齐特，一种被认为可以减弱可卡因和海洛因的强化作用的药物，在不干扰剂量-反应关系的情况下改变了功能;匹莫齐特可靠地减少了连续可卡因输注之间的时间，剂量范围为匹莫齐特的4倍。匹莫齐特对海洛因自我给药的影响在统计学上不显著，并且在最高测试剂量下破坏了反应。因此，这种模式提供了一个会话内评估的剂量依赖性的可卡因和海洛因的强化行动的持续时间，这种评估是敏感的静脉注射药物强化的至少一个挑战。
Rats were trained to intravenously self-administer unit doses of cocaine or heroin. Constant supplemental infusion of a portion of each rat''s mean hourly intake increased the mean time between successive infusins, but the effect was not statistically reliable from the data of a small sample of animals. A variable dose per infusion (VDI) paradigm was developed which enabled testing of several unit doses of cocaine or heroin within single test sessions. Unit doses of 0.5, 1.0, and 2.0 mg/kg of cocaine or 0.025, 0.05, and 0.1 mg/kg of heroin were made available with equal frequency but in unpredictable sequence to independent groups of rats. The mean time between successive infusions was linearly related to the log dose of the preceding infusion in each case. Pimozide, a drug thought to attenuate the reinforcing effects of both cocaine and heroin, shifted the functions without disturbing the dose-response relations; pimozide reliably decreased the time between successive cocaine infusions across a 4-fold range of pimozide doses. The effect of pimozide on heroin self-administration was not statistically significant and disrupted responding at the highest dose tested. This paradigm thus offers a within-session assessment of the dose-dependent duration of reinforcing actions of cocaine and heroin, and this assessment is sensitive to at least one challenge of intravenous drug reinforcement.