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Rationale: Preclinical and clinical studies suggest the potential use of memantine in the treatment of binge eating disorder. The aim of this study was to further investigate the mechanisms by which memantine influences the motivational aspects of ingestion through the analysis of licking microstructure. To interpret treatment effects in relation to drug action at specific functionally relevant times, we compared the effect of two different administration schedules. Methods: Memantine was administered daily for a week, either 1 hour before or immediately after a 30-min daily session. The effects on the microstructure of licking for a 10% sucrose solution in rats were examined in the course of treatment and for 15 days after treatment discontinuation. Results: Treatment before testing reduced ingestion due to reduced burst size, and increased latency in the first session. However, a progressive increase in burst number across sessions led to a full recovery of ingestion levels by the end of treatment. Daily post-session administration induced a dramatic decrease of activation of licking behaviour, indicated by reduced burst number, accompanied to reduced burst size. A slow recovery of ingestion took place after treatment discontinuation. Conclusion: These results suggest a reduced hedonic/reward evaluation response, an effect likely due to NMDA receptor blockade occurring during the testing time, and support the hypothesis that memantine interferes with the hedonic/non-homeostatic mechanisms regulating food-intake and food seeking. The effect of post-session administration might be explained by the development of conditioned taste aversion.

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