Effects of continuous nicotine infusion on nicotine self-administration in rats: relationship between Continuously infused and self-administered nicotine doses and serum concentrations
Effects of continuous nicotine infusion on nicotine self-administration in rats: relationship between Continuously infused and self-administered nicotine doses and serum concentrations
复制标题
DOI：
10.1007/s00213-003-1539-2
复制
发表时间：
2003-11-01
影响因子：
3.4
通讯作者：
Pentel, PR
中科院分区：
文献类型：
--
作者：
LeSage, MG;Keyler, DE;Pentel, PR
理由：尼古丁替代疗法（NRT）对戒烟的疗效有限。这种有限效果的一个原因可能是NRT提供的典型血清尼古丁浓度与吸烟所达到的动脉尼古丁峰值浓度不匹配。目的：本研究的目的是确定以产生与大鼠尼古丁自我给药（NSA）相关的估计动脉尼古丁峰值浓度相匹配的速率持续尼古丁输注是否比低输注速率对NSA产生更大的抑制。方法：采用不同剂量（1.0、3.0、8.0 mg/kg / d）的尼古丁静脉滴注方法，对同时自吸尼古丁（0.03 mg/kg / d）的大鼠（23 h）和自吸可卡因（0.17 mg/kg / d）的大鼠（2 h）进行连续尼古丁滴注。结果：持续尼古丁输注抑制NSA呈速率相关。在每天1.0、3.0和8.0 mg/kg的输注速率下，NSA分别被抑制了17%、50%和73%。在8.0 mg/kg /天的输注速率下，静脉血清尼古丁浓度等于与NSA相关的动脉峰值浓度，与低输注速率相比，对NSA的抑制程度更大。8.0 mg/kg /天的尼古丁输注速率对可卡因维持应答无影响，表明其对抑制NSA的作用是特异性的。这种输注速率提供了超过700%的NSA尼古丁替代的平均百分比。两种最高输注率抑制后的NSA重新获得与盐水消失后的重新获得相比延迟。结论：持续尼古丁输注产生了与输注速率相关的NSA抑制，当输注尼古丁剂量和静脉血清浓度显著高于人类NRT相关的典型水平时，这种抑制效果最大。
Rationale: The efficacy of nicotine replacement therapy (NRT) for smoking cessation is limited. One reason for this limited efficacy may be that typical serum nicotine concentrations provided by NRT do not match the peak arterial nicotine concentrations achieved from smoking. Objective: The purpose of the present study was to determine whether continuous nicotine infusion at a rate producing serum nicotine concentrations that match the estimated peak arterial nicotine concentrations associated with nicotine self-administration (NSA) in rats produces greater suppression of NSA than lower infusion rates. Methods: The effects of continuous nicotine infusion were studied by intravenously administering nicotine at various rates (1.0, 3.0, and 8.0 mg/kg per day) to rats concurrently self-administering nicotine (0.03 mg/ kg per infusion) during 23-h sessions or cocaine (0.17 mg/ kg per infusion) during 2-h sessions. Results: Continuous nicotine infusion suppressed NSA in a rate-related fashion. NSA was suppressed by 17, 50, and 73% at infusion rates of 1.0, 3.0 and 8.0 mg/kg per day, respectively. The 8.0-mg/kg per day infusion rate, which provided venous serum nicotine concentrations equaling the peak arterial concentrations associated with NSA, suppressed NSA to a greater extent than lower infusion rates. The 8.0-mg/kg per day nicotine infusion rate had no effect on cocaine-maintained responding, demonstrating that its effects were specific for suppression of NSA. This infusion rate provided a mean percentage replacement of nicotine from NSA of more than 700%. Reacquisition of NSA after suppression by the two highest infusion rates was delayed compared with reacquisition after saline extinction. Conclusions: Continuous nicotine infusion produced an infusion rate-related suppression of NSA that was greatest when the infusion provided nicotine doses and venous serum concentrations substantially higher than those typically associated with NRT in humans.