Skjei Karen L, Markou Athina
Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Psychopharmacology (Berl). 2003 Jul;168(3):280-92. doi: 10.1007/s00213-003-1414-1. Epub 2003 Apr 24.
The aversive aspects of nicotine withdrawal contribute to high relapse rates to tobacco smoking after cessation attempts.
To investigate the influence of nicotine dose, duration of nicotine exposure, and withdrawal history on the severity of nicotine withdrawal in rats, as assessed by brain stimulation reward thresholds and somatic signs of withdrawal.
Repeated spontaneous and precipitated withdrawals were investigated through four successive removals of osmotic minipumps delivering nicotine/saline, or with daily injections of the nicotinic receptor antagonist dihydro-beta-erythroidine during chronic nicotine/saline exposure, respectively. The effects of dose and duration of exposure were investigated using minipumps of varying duration delivering different nicotine doses.
Increased duration of nicotine exposure: a). prolonged the duration but did not alter the magnitude of withdrawal-associated threshold elevations; b). increased somatic signs early during withdrawal. Increased total nicotine exposure (i.e. increased dose and exposure duration) increased the duration of threshold elevations (no effect on magnitude) but had no effect on somatic signs. Neither repeated spontaneous nor repeated precipitated withdrawals altered the magnitude of withdrawal significantly.
Increases in total nicotine dose resulted in increased severity of the affective aspects of withdrawal. Further, continuous drug exposure resulted in longer lasting withdrawal than intermittent administration even when the total nicotine dose was the same. There was no correlation between threshold elevations and somatic signs of withdrawal. In conclusion, the severity of nicotine withdrawal is mitigated by characteristics of the drug exposure regimen such as drug dose, duration of exposure and whether exposure is continuous or intermittent.
尼古丁戒断的厌恶方面导致戒烟尝试后吸烟复发率很高。
通过脑刺激奖赏阈值和戒断的躯体症状评估，研究尼古丁剂量、尼古丁暴露持续时间和戒断史对大鼠尼古丁戒断严重程度的影响。
分别通过连续四次移除输送尼古丁/生理盐水的渗透微型泵，或在慢性尼古丁/生理盐水暴露期间每日注射烟碱受体拮抗剂二氢β-刺桐碱，研究反复的自发和诱发戒断。使用输送不同尼古丁剂量的不同持续时间的微型泵研究暴露剂量和持续时间的影响。
尼古丁暴露持续时间增加：a）延长了持续时间，但未改变与戒断相关的阈值升高幅度；b）在戒断早期增加了躯体症状。总尼古丁暴露增加（即剂量增加和暴露持续时间增加）增加了阈值升高的持续时间（对幅度无影响），但对躯体症状无影响。反复的自发戒断和反复的诱发戒断均未显著改变戒断幅度。
总尼古丁剂量增加导致戒断情感方面的严重程度增加。此外，即使总尼古丁剂量相同，持续药物暴露导致的戒断持续时间比间歇性给药更长。阈值升高与戒断的躯体症状之间没有相关性。总之，尼古丁戒断的严重程度可通过药物暴露方案的特征（如药物剂量、暴露持续时间以及暴露是连续还是间歇性）得到缓解。
