Determination of behaviorally effective tobacco constituent doses in rats.

Abstract

While nicotine has been established as the primary addictive drug that promotes tobacco use, recent peer-reviewed studies suggest that tobacco smoke contains additional chemical constituents that may have addictive potential. Additional research is necessary to determine the addictive potential of these tobacco constituents individually and in combination with tobacco smoke condensate; however, the behaviorally effective constituent doses necessary to conduct such studies are unclear. The primary objective of this study was to conduct behavioral studies in adult rats to determine the relevant behaviorally effective doses of the tobacco constituents, cotinine, myosmine, and anatabine to be used in future studies assessing the addictive potential of these compounds. Separate groups of adult male Sprague Dawley rats were treated with vehicle, nicotine, or various doses of cotinine, mysomine, or anatabine. Effects on locomotor activity were measured in 10-min bins for 60min. Nicotine (0.8mg/kg) produced a biphasic effect on locomotor activity, with hypoactivity during the first 10min and hyperactivity at 40-50min. In contrast, cotinine (0.1mg/kg) and myosmine (10-50mg/kg) decreased activity without a later increase. Anatabine significantly increased locomotor activity at 1mg/kg, but decreased it at 10mg/kg. Prominent effects on overt behavior were observed at anatabine doses of 10mg/kg and above. Nicotine, cotinine, myosmine, and anatabine produced distinct time- and dose-dependent patterns of effects on locomotor activity. Results from the study will aid in the selection of relevant doses for future studies assessing the addictive potential of these non-nicotine tobacco constituents.