An analysis of response to nicotine infusion using an automated radiotelemetry system

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.