Daily memantine treatment blunts hedonic response to sucrose in rats
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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.
Memantine was administered daily for a week, either 1 h 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.
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.
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.
KeywordsMemantine Licking microstructure Anhedonia Activation Conditioned taste aversion
The present study was funded by the Fondazione di Sardegna, Sassari, Italy.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- De Chiara L, Serra G, Koukopoulos AE, Koukopoulos A, Serra G (2014) Memantine in the treatment and prophylaxis of bipolar type II mood disorder and co-morbid eating disorder: a case report. Riv Psichiatr 49:192–194Google Scholar
- Freeman CR, Zehra A, Ramirez V, Wiers CE, Volkow ND, WangGJ (2018) Impact of sugar on the body, brain, and behavior. Front Biosci 23:2255–2266Google Scholar
- Lu S, Nasrallah HA (2018) The use of memantine in neuropsychiatric disorders: an overview. Ann Clin Psychiatry 30:234–248Google Scholar
- Rammes G, Rupprecht R, Ferrari U, Zieglgänsberger W, Parsons CG (2001) The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner. Neurosci Lett 306:81–84CrossRefGoogle Scholar
- Sani G, Serra G, Kotzalidis GD, Romano S, Tamorri SM, Manfredi G, Caloro M, Telesforo CL, Caltagirone SS, Panaccione I, Simonetti A, Demontis F, SerraG GP (2012) The role of memantine in the treatment of psychiatric disorders other than the dementias: a review of current preclinical and clinical evidence. CNS Drugs 26:663–690CrossRefGoogle Scholar
- Smith KL, Rao RR, Velázquez-Sánchez C, Valenza M, Giuliano C, Everitt BJ, Sabino V, Cottone P (2015) The uncompetitive N-methyl-D-aspartate antagonist memantine reduces binge-like eating, food-seeking behavior, and compulsive eating: role of the nucleus accumbens shell. Neuropsychopharmacology 40:1163–1171CrossRefGoogle Scholar
- Vardigan JD, Huszar SL, McNaughton CH, Hutson PH, Uslaner JM (2010) MK-801 produces a deficit in sucrose preference that is reversed by clozapine, D-serine, and the metabotropic glutamate 5 receptor positive allosteric modulator CDPPB: relevance to negative symptoms associated with schizophrenia? Pharmacol Biochem Behav 95:223–229CrossRefGoogle Scholar
- Wise RA (1982a) Common neural basis for stimulation reward, drug reward and food reward. In: Hoebel BG, Novin D (eds) The neural basis of feeding and reward. Haer Institute for Electrophysiological Research, Brunswick, ME, pp 445–454Google Scholar