Rationale

While it is known that tobacco use varies across the 24-h day, the time-of-day effects are poorly understood. Findings from several previous studies indicate a potential role for melatonin in these time-of-day effects; however, the specific underlying mechanisms have not been well characterized. Understanding of these mechanisms may lead to potential novel smoking cessation treatments.

Objective

The objective of this study is examine the role of melatonin and melatonin receptors in nicotine free-choice consumption

Methods

A two-bottle oral nicotine choice paradigm was utilized with melatonin supplementation in melatonin-deficient mice (C57BL/6J) or without melatonin supplementation in mice proficient at melatonin synthesis (C3H/Ibg) compared to melatonin-proficient mice lacking both or one of the high-affinity melatonin receptors (MT 1 and MT 2 ; double-null mutant DM, or MT 1 or MT 2 ). Preference for bitter and sweet tastants also was assessed in wild-type and MT 1 and MT 2 DM mice. Finally, home cage locomotor monitoring was performed to determine the effect of melatonin administration on activity patterns.

Results

Supplemental melatonin in drinking water significantly reduced free-choice nicotine consumption in C57BL/6J mice, which do not produce endogenous melatonin, while not altering activity patterns. Independently, genetic deletion of both MT 1 and MT 2 receptors in a melatonin-proficient mouse strain (C3H) resulted in significantly more nicotine consumption than controls. However, single genetic deletion of either the MT 1 or MT 2 receptor alone did not result in increased nicotine consumption. Deletion of MT 1 and MT 2 did not impact taste preference.

Conclusions