Robinson S F, Pauly J R, Marks M J, Collins A C
Institute for Behavioral Genetics, University of Colorado, Boulder 80309.
Psychopharmacology (Berl). 1994 Jun;115(1-2):115-20. doi: 10.1007/BF02244760.
Previous studies from our laboratory have demonstrated that chronic nicotine infusion evokes tolerance to nicotine injected IP several hours after withdrawal from chronic infusion. This method may introduce problems related to withdrawal reactions and to stress associated with handling of the animals. The studies reported here measured tolerance to nicotine in mice using an automated radiotelemetry system. DBA/2 mice were infused intravenously with saline for 4 days followed by infusion of a 4 mg/kg per h dose of nicotine for 7 days. After the nicotine treatment, the mice were infused with saline for 7 days. The nicotine was infused continuously or in four 1 mg/kg pulses, two 2 mg/kg pulses or one 4 mg/kg pulse each hour. Home cage activity and body temperature were measured throughout the treatment periods using a radiotelemetry system. Nicotine infusion produced an abrupt decrease in body temperature and activity, but this effect was totally reversed within 12 h in the continuously infused and four infusions/h treatment groups. Mice that received one or two infusions/h also showed a rapid response to nicotine that was reversed as treatment proceeded, but nicotine continued to produce a measurable effect for several days. After nicotine withdrawal, temperature and activity returned to predrug infusion values in all of the groups except those infused once per hour. This group showed depressed activity for a minimum of 3 days after nicotine treatment stopped. Thus, the kinetics of nicotine administration affected the intensity of response during continued treatment as well as activity after cessation of chronic treatment.
我们实验室之前的研究表明，在从慢性尼古丁输注撤药数小时后，慢性尼古丁输注会引发对腹腔注射尼古丁的耐受性。这种方法可能会带来与撤药反应以及与动物处理相关的应激有关的问题。此处报道的研究使用自动无线电遥测系统测量了小鼠对尼古丁的耐受性。给DBA/2小鼠静脉输注生理盐水4天，随后以每小时4毫克/千克的剂量输注尼古丁7天。尼古丁处理后，给小鼠输注生理盐水7天。尼古丁以连续方式输注，或以每小时四个1毫克/千克脉冲、两个2毫克/千克脉冲或一个4毫克/千克脉冲的方式输注。在整个治疗期间，使用无线电遥测系统测量笼内活动和体温。尼古丁输注使体温和活动突然下降，但在连续输注组和每小时输注四次的治疗组中，这种效应在12小时内完全逆转。每小时接受一次或两次输注的小鼠对尼古丁也表现出快速反应，随着治疗的进行这种反应会逆转，但尼古丁在数天内仍会产生可测量的效应。尼古丁撤药后，除每小时输注一次的组外，所有组的体温和活动都恢复到给药前输注时的值。该组在尼古丁治疗停止后至少3天内活动受到抑制。因此，尼古丁给药的动力学影响了持续治疗期间的反应强度以及慢性治疗停止后的活动。
