A comparison of nicotine and cocaine self-administration in the dog: fixed-ratio and progressive-ratio schedules of intravenous drug infusion.
A comparison of nicotine and cocaine self-administration in the dog: fixed-ratio and progressive-ratio schedules of intravenous drug infusion.
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狗尼古丁和可卡因自我给药的比较：静脉药物输注的固定比例和渐进比例方案。
DOI：
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发表时间：
1983
影响因子：
3.5
通讯作者：
S. Goldberg
中科院分区：
文献类型：
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作者：
M. Risner;S. Goldberg
比格犬按下一个杠杆，在15个反应固定比例的计划下静脉注射尼古丁或可卡因或水。每次固定比例试验后有4分钟的暂停时间，在连续16次固定比例试验后，每天的训练结束。尼古丁和可卡因均为高于生理盐水水平的自我注射，最大注射次数为尼古丁30微克/千克和可卡因100微克/千克。应答率首先增加，在10至30微克/公斤/次输注时达到最大值，然后随着尼古丁或可卡因的剂量在3至300微克/公斤/次输注之间变化而下降。可卡因自我给药组的应答率和每次注射次数均高于尼古丁自我给药组。用烟碱拮抗剂甲美胺（1.0 mg/kg静脉注射）进行连续7次的抑制治疗，降低了尼古丁维持的反应水平，与用生理盐水代替药物时所见的水平没有什么不同。用甲美胺治疗抑郁症对可卡因和水维持反应均无影响。第二组比格犬在静脉注射尼古丁（50-400微克/公斤/次输注）或可卡因（200-1600微克/公斤/次输注）的情况下按压杠杆，其中固定比例要求每天增加（即渐进比例计划）。维持反应的最大固定比值值首先随着每次注射剂量的增加而增加，然后在最高剂量时保持不变或下降。可卡因的固定比值值比尼古丁高得多，但尼古丁的最大固定比值值远高于生理盐水。在第三组比格犬中测量了静脉注射尼古丁（3、30或300微克/公斤）或甲胺（1.0毫克/公斤）对心率、直肠温度和瞳孔直径的影响。尼古丁在所有三个生理参数中产生剂量和时间相关的变化；甲胺的效果明显大于尼古丁。
Beagle dogs pressed a lever under a 15-response fixed-ratio schedule of i.v. nicotine or cocaine infusion or water presentation. A 4-min time-out period followed each fixed-ratio trial and each daily session ended after 16 successive fixed-ratio trials. Both nicotine and cocaine were self-administered above saline levels, with the maximum number of infusions occurring at a dose of 30 micrograms/kg of nicotine and 100 micrograms/kg of cocaine. Rates of responding first increased, reaching a maximum at 10 to 30 micrograms/kg/infusion and then decreased, as the dose of nicotine or cocaine was varied between 3 and 300 micrograms/kg/infusion. The rate of responding and number of infusions obtained per session were higher under the schedule of cocaine self-administration than under the schedule of nicotine self-administration. Presession treatment with the nicotinic antagonist, mecamylamine (1.0 mg/kg i.v.), for seven consecutive sessions, decreased nicotine-maintained responding to levels not unlike those seen when saline was substituted for drug. Neither cocaine- nor water-maintained responding was affected by presession treatment with mecamylamine. A second group of beagle dogs pressed a lever under a schedule of i.v. nicotine (50-400 micrograms/kg/infusion) or cocaine (200-1600 micrograms/kg/infusion) infusion in which the fixed-ratio requirement was increased daily (i.e., a progressive-ratio schedule). The maximum fixed-ratio value at which responding was maintained first increased as the dose per infusion increased and then, at the highest dose, either remained the same or decreased. Cocaine maintained considerably higher fixed-ratio values than did nicotine, but maximum fixed-ratio values for nicotine were well above those seen with saline. The effects of i.v. nicotine (3, 30 or 300 micrograms/kg) or mecamylamine (1.0 mg/kg) on heart rate, rectal temperature and pupillary diameter were measured in a third group of beagle dogs. Nicotine produced dose- and time-related changes in all three physiological parameters; the effects of mecamylamine were considerably greater than those seen with nicotine.