title: Differential effects of a short-term high-fat diet in an animal model of depression in rats treated with the 5-HT3 receptor antagonist, ondansetron, the 5-HT3 receptor agonist, 2-methyl-5-HT, and the SSRI, fluoxetine.
abstract: Investigation into the effects of a high-fat diet on depression in the context of 5-HT3 receptor function is important given 5-HT3 antagonism may represent a novel candidate for drug discovery. To more fully understand the relationship between the 5-HT3 receptor system, depression, and high-fat intake, our main interest was to study the short-term effects of a high-fat diet on the 5-HT3 receptor antagonist, ondansetron, and the 5-HT3 receptor agonist, 2-methyl-5-HT, as well as the SSRI, fluoxetine, in an animal model of depression. Male Sprague Dawley rats were fed either a standard diet (11% fat) or a high-fat diet (32.5% fat) for seven days then treated with either fluoxetine (10mg/kg, ip), ondansetron (1mg/kg, ip), 2-methyl-5-HT (3mg/kg, ip), fluoxetine+ondansetron or, 2-methyl-5-HT+ondansetron prior to the Forced Swim Test. In the standard diet group, treatment with the 5HT3 receptor agonist, 2-methyl-5-HT, served to significantly decrease time of immobility as compared to controls thus showing anti-depressive-like effects. Treatment with the 5-HT3 receptor antagonist, ondansetron, served to enhance the anti-depressive like effects of the SSRI, fluoxetine, as treatment with both the SSRI and 5-HT3 receptor antagonist dramatically decreased immobility. Importantly, in the high-fat diet groups, a week of high-fat intake served to: 1) counteract the anti-depressive-like effect of the SSRI, fluoxetine, 2) reverse the anti-depressive-like effect of the 5HT3 receptor agonist, 2-methyl-5-HT and 3) provide protection against the depressive-like effects induced by the Forced Swim Test as rats fed a high-fat diet displayed the lowest amounts of immobility. In the aggregate, these data suggest that both SSRIs and the 5HT3 receptor system are affected by short-term high-fat intake and that a short-term high-fat diet protects against depressive-like effects in an animal model of depression.
authors.affiliation: Department of Psychology, Behavioral Neuroscience Laboratory, California State University, Bakersfield, Bakersfield, CA 93311-1099, USA. Electronic address: isumaya@CSUB.edu.
authors.forename: Isabel C
authors.initials: IC
authors.lastname: Sumaya
authors.affiliation: Department of Psychology, Behavioral Neuroscience Laboratory, California State University, Bakersfield, Bakersfield, CA 93311-1099, USA.
authors.forename: Dee
authors.initials: D
authors.lastname: Bailey
authors.affiliation: Department of Psychology, Behavioral Neuroscience Laboratory, California State University, Bakersfield, Bakersfield, CA 93311-1099, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Catlett
mesh_terms: D000818:Animals; D003863:Depression / Q000178:diet therapy* / Q000188:drug therapy; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000627:therapeutic use*; D008297:Male; D017294:Ondansetron / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
chemical_list: D005473:Fluoxetine; D017294:Ondansetron; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors
keywords: 5HT3 receptors; Depression; Forced Swim Test; High-fat diets; SSRIs