title: GS 455534 selectively suppresses binge eating of palatable food and attenuates dopamine release in the accumbens of sugar-bingeing rats.
abstract: Binge eating palatable foods has been shown to have behavioral and neurochemical similarities to drug addiction. GS 455534 is a highly selective reversible aldehyde dehydrogenase 2 inhibitor that has been shown to reduce alcohol and cocaine intake in rats. Given the overlaps between binge eating and drug abuse, we examined the effects of GS 455534 on binge eating and subsequent dopamine release. Sprague-Dawley rats were maintained on a sugar (experiment 1) or fat (experiment 2) binge eating diet. After 25 days, GS 455534 was administered at 7.5 and 15 mg/kg by an intraperitoneal injection, and food intake was monitored. In experiment 3, rats with cannulae aimed at the nucleus accumbens shell were maintained on the binge sugar diet for 25 days. Microdialysis was performed, during which GS 455534 15 mg/kg was administered, and sugar was available. Dialysate samples were analyzed to determine extracellular levels of dopamine. In experiment 1, GS 455534 selectively decreased sugar intake food was made available in the Binge Sugar group but not the Ad libitum Sugar group, with no effect on chow intake. In experiment 2, GS 455534 decreased fat intake in the Binge Fat group, but not the Ad libitum Fat group, however, it also reduced chow intake. In experiment 3, GS 455534 attenuated accumbens dopamine release by almost 50% in binge eating rats compared with the vehicle injection. The findings suggest that selective reversible aldehyde dehydrogenase 2 inhibitors may have the therapeutic potential to reduce binge eating of palatable foods in clinical populations.
authors.affiliation: aDepartment of Psychology, Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey bLieber Institute for Brain Development, Baltimore, Maryland cDepartment of Psychiatry, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, Florida dGilead Sciences, Palo Alto, California, USA.
authors.forename: Miriam E
authors.initials: ME
authors.lastname: Bocarsly
authors.forename: Bartley G
authors.initials: BG
authors.lastname: Hoebel
authors.forename: Daniel
authors.initials: D
authors.lastname: Paredes
authors.forename: Isabell
authors.initials: I
authors.lastname: von Loga
authors.forename: Susan M
authors.initials: SM
authors.lastname: Murray
authors.forename: Miaoyuan
authors.initials: M
authors.lastname: Wang
authors.forename: Maria P
authors.initials: MP
authors.lastname: Arolfo
authors.forename: Lina
authors.initials: L
authors.lastname: Yao
authors.forename: Ivan
authors.initials: I
authors.lastname: Diamond
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Avena
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D002032:Bulimia / Q000188:drug therapy* / Q000378:metabolism; D004041:Dietary Fats; D019422:Dietary Sucrose; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C550386:CVT-10216; D004041:Dietary Fats; D019422:Dietary Sucrose; D004791:Enzyme Inhibitors; D007529:Isoflavones; D024101:Mitochondrial Proteins; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat; D004298:Dopamine