AN ANALYSIS OF RESPONSE TO NICOTINE INFUSION USING AN AUTOMATED RADIOTELEMETRY SYSTEM

Previous studies from our laboratory have demonstrated that chronic ni cotine infusion evokes tolerance to nicotine injected IP several hours after withdrawal from chronic infusion. This method may introduce pro blems related to withdrawal reactions and to stress associated with ha ndling 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 infusio n of a 4 mg/kg per h dose of nicotine for 7 days. After the nicotine t reatment, the mice were infused with saline for 7 days. The nicotine w as 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 temperatur e were measured throughout the treatment periods using a radiotelemetr y system. Nicotine infusion produced an abrupt decrease in body temper ature and activity, but this effect was totally reversed within 12 h i n 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 contin ued to produce a measurable effect for several days. After nicotine wi thdrawal, temperature and activity returned to predrug infusion values in all of the groups except those infused once per hour. This group s howed depressed activity for a minimum of 3 days after nicotine treatm ent stopped. Thus, the kinetics of nicotine administration affected th e intensity of response during continued treatment as well as activity after cessation of chronic treatment.