Intravenous nicotine self-administration in rats: effects of mecamylamine, hexamethonium and naloxone
Intravenous nicotine self-administration in rats: effects of mecamylamine, hexamethonium and naloxone
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DOI：
10.1007/s00213-005-0054-z
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发表时间：
2006-02-01
影响因子：
3.4
通讯作者：
Mele, PC
中科院分区：
文献类型：
--
作者：
DeNoble, VJ;Mele, PC
在24小时内对18只大鼠的杠杆按压速率和模式进行了研究，其中响应导致静脉输注尼古丁。有四种迹象表明尼古丁具有积极的强化作用：（1）与生理盐水可用时相比，尼古丁反应相关时的杠杆按压次数更多;（2）导致尼古丁输注的杠杆反应次数多于对照杠杆;（3）当尼古丁非偶然输送时，偶然尼古丁输注次数系统性减少;和（4）作为剂量函数的杠杆按压频率的系统变化。在固定比例1（FR 1）方案下，输注次数随着尼古丁剂量的降低（64、32、16和8 μ g/kg输注）而先增加后减少，尼古丁摄入量（mg/kg，每24小时一次）与输注剂量直接相关。随着FR大小从1增加到6，杠杆按压次数增加，输注次数（32 μ g/kg）保持稳定。当FR值大于6时，杠杆按压次数和输注次数均减少。将美加明（0.75、1.5和3.0 mg/kg，s.c.）以剂量相关方式减少输注次数。六烃季铵（1.5和3.0 mg/kg，s.c.）或纳洛酮（0.75、1.5和3.0 mg/kg，s.c.）没有改变尼古丁自我给药的会话内或会话间模式。在本实验的条件下，尼古丁作为一种有效的催泪剂，并且该行为被证明对FR大小和输注剂量都敏感。此外，结果表明，尼古丁自我管理涉及中央烟碱受体和阿片受体拮抗剂对尼古丁的强化作用在大鼠没有影响。
The rate and pattern of lever pressing were studied in 18 rats during 24-h sessions in which responding resulted in intravenous infusions of nicotine. There were four indications of the positive reinforcing effect of nicotine: (1) a greater number of lever presses when nicotine was response-contingent compared to when saline was available; (2) a greater number of responses on the lever resulting in an infusion of nicotine than on the control lever; (3) systematic decreases in the number of contingent nicotine infusions when nicotine was delivered noncontingently; and (4) systematic changes in the frequency of lever pressing as a function of dose. Under a fixed ratio 1 (FR 1) schedule, the number of infusions first increased and then decreased as the dose of nicotine was decreased (64, 32, 16, and 8 mu g/kg infusion) and nicotine intake (mg/kg every 24 h) was directly related to the infusion dose. As the FR size was increased from 1 to 6, the number of lever presses increased and the number of infusions (32 mu g/kg) remained stable. At FR values greater than 6, both the number of lever presses and infusions decreased. Presession injections of mecamylamine (0.75, 1.5, and 3.0 mg/kg, s.c.) decreased the number of infusions in a dose-related manner. Presession injections of hexamethonium (1.5 and 3.0 mg/kg, s.c.) or naloxone (0.75, 1.5, and 3.0 mg/kg, s.c.) did not alter the within- or between-session patterns of nicotine self-administration. Under the conditions of the present experiment, nicotine served as an effective reinforcer and the behavior was shown to be sensitive to both FR size and infusion dose. In addition, the results suggest that nicotine self-administration involves central nicotinic receptors and that opioid receptor antagonism has no effect on nicotine's reinforcing effects in rats.