Food-induced reinforcement is abrogated by the genetic deletion of the MT₁ or MT₂ melatonin receptor in C3H/HeN mice.

Palatable food is known for its ability to enhance reinforcing responses. Studies have suggested a circadian variation in both drug and natural reinforcement, with each following its own time course. The goal of this study was to determine the role of the MT₁ and MT₂ melatonin receptors in palatable snack food-induced reinforcement, as measured by the conditioned place preference (CPP) paradigm during the light and dark phases. C3H/HeN wild-type mice were trained for snack food-induced CPP at either ZT 6 - 8 (ZT: Zeitgeber time; ZT 0 = lights on), when endogenous melatonin levels are low, or ZT 19 - 21, when melatonin levels are high. These time points also correspond to the high and low points for expression of the circadian gene Period1, respectively. The amount of snack food (chow, Cheetos®, Froot Loops® and Oreos®) consumed was of similar magnitude at both times, however only C3H/HeN mice conditioned to snack food at ZT 6 - 8 developed a place preference. C3H/HeN mice with a genetic deletion of either the MT₁ (MT₁KO) or MT₂ (MT₂KO) receptor tested at ZT 6 - 8 did not develop a place preference for snack food. Although the MT₂KO mice showed a similar amount of snack food consumed when compared to wild-type mice, the MT₁KO mice consumed significantly less than either genotype. We conclude that in our mouse model snack food-induced CPP is dependent on time of day and the presence of the MT₁ or MT₂ receptors, suggesting a role for melatonin and its receptors in snack food-induced reinforcement.

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