Magnitude of open-field thigmotaxis during mecamylamine-precipitated nicotine withdrawal in rats is influenced by mecamylamine dose, duration of nicotine infusion, number of withdrawal episodes, and age

Abstract

Relief from increases in anxiety during nicotine withdrawal contributes to tobacco addiction. While a variety of anxiogenic stimuli elicit avoidance of the center of an open field (thigmotaxis) in rodents, effects of nicotine withdrawal on thigmotaxis have not been studied extensively. The goal of this study was to evaluate determinants of increases in thigmotaxis during mecamylamine-precipitated nicotine withdrawal in rats. We evaluated several variables implicated in severity of other measures of precipitated nicotine withdrawal: mecamylamine dose, duration of nicotine infusion, number of withdrawal episodes, and age. In Experiment 1, mecamylamine elicited increases in thigmotaxis in adult rats receiving a chronic nicotine infusion (3.2 mg/kg/day for >7 days) at only the highest mecamylamine dose tested (4.0 mg/kg). In Experiment 2, repeated administration of 4.0 mg/kg mecamylamine throughout the course of a 2-week chronic nicotine infusion (3.2 mg/kg/day) did not affect thigmotaxis when administered following 2 days of the infusion, but elicited significant increases in thigmotaxis at longer infusion durations. In Experiment 3, adolescents tested under the same protocol used in adults in Experiment 2 did not exhibit increased thigmotaxis at any point during the 2-week nicotine infusion, even though we used higher nicotine doses (4.7 or 6.4 mg/kg/day) to account for the faster metabolism of nicotine in adolescents compared to adults. Our findings provide the first systematic characterization of determinants of increases in thigmotaxis during precipitated nicotine withdrawal in rats. Further use of this model may be useful for characterizing the mechanisms underlying the anxiogenic component of nicotine withdrawal.