Antagonism of glutamatergic NMDA and mGluR5 receptors decreases consumption of food in baboon model of binge-eating disorder.
Excessive consumption of highly palatable foods may contribute to the development of weight gain. Therefore medications that selectively suppress eating of such foods would be useful in clinical practice. We compared the effects of the glutamatergic antagonists memantine and MTEP to dexfenfluramine in baboons given periodic access to highly palatable food and ad libitum access to a standard chow diet. Three days a week baboons received a sugar-coated candy during the first meal and standard standard-diet chow pellets were available in subsequent meals. All baboons derived a greater amount of energy from the single single-candy meal than from the standard diet across an entire day. Pre-treatment with dexfenfluramine, memantine, and MTEP produced decreases in candy consumption without altering candy-seeking behaviour. At the same time, dexfenfluramine and memantine, but not MTEP, produced a decrease in seeking and consumption of standard chow pellets. Both memantine and MTEP are promising agents for the treatment of obesity.
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, New York, NY 10032, USA. amb107@columbia.edu
Adam
A
Bisaga
Wojciech
W
Danysz
Richard W
RW
Foltin
D000818:Animals; D001066:Appetite / Q000187:drug effects; D052018:Bulimia Nervosa / Q000188:drug therapy* / Q000523:psychology*; D002182:Candy; D003216:Conditioning, Operant / Q000187:drug effects; D003259:Consummatory Behavior / Q000187:drug effects; D020372:Dexfenfluramine / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D008297:Male; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use; D048548:Papio cynocephalus; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D012727:Sex Characteristics; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects
C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017366:Serotonin Receptor Agonists; D013844:Thiazoles; D020372:Dexfenfluramine; D008559:Memantine