The Multiple Bottle Effect Is Overridden in Male and Female Rats by Simultaneous Presentation of Two Oral Nicotine Solutions

BACKGROUND: Studies on the oral route of nicotine administration in rodents make important contributions to our understanding of human nicotine use, and alternative approaches to smoking cessation. While environmental availability of oral nicotine contributes to voluntary intake and appears to drive consumption initially, solution concentration may exert more control over intake with continued exposure. Further, it is believed that female rodents consume more nicotine and show greater motivation to obtain it than males. OBJECTIVES: The purpose of our study was to determine voluntary oral nicotine intake patterns following continuous exposure to relatively high concentrations in male and female rats, employing a multiple bottle approach, and to describe the relationship between oral nicotine consumption and sera cotinine. METHODS: Using five bottles, adult Sprague-Dawley rats were given continuous access to water and 15 μg/ml nicotine solutions or water and 15 and 30 μg/ml nicotine solutions for 2 weeks; blood serum was analyzed for cotinine. RESULTS: Rats consistently consumed oral nicotine and female rats ingested more nicotine than males, even at relatively high concentrations. Yet, when both concentrations were presented simultaneously, oral nicotine intake did not exceed that of water, thus overriding an environmental, or multiple-bottle, effect. Cotinine was systemically circulated following first-pass hepatic metabolism of nicotine at early, but not at later stages of nicotine exposure. CONCLUSIONS: Our findings suggest rats will readily and voluntarily ingest considerably higher doses of nicotine than previously reported resulting in initial systemic cotinine, and trends toward sex differences are mitigated by solution concentration.