title: Regulation of emotional response in juvenile monkeys treated with fluoxetine: MAOA interactions.
abstract: Juvenile male rhesus macaques received therapeutic doses of fluoxetine daily from one to three years of age and were compared to vehicle-treated controls (N=16/group). Genotyping for monoamine oxidase A (MAOA) polymorphisms was used to form subgroups (N=8) with high and low expression of the gene. Behavioral responses were scored during 30-second exposures to pictures differing in affective content. As expected from its therapeutic effect, fluoxetine decreased the behavioral response to emotionally evocative pictures. A 44% reduction in number of expressive behaviors was seen, but only in subjects with low expression MAOA polymorphisms. In general, this effect occurred for pictures of varying affective content and was not due to altered occurrence of one specific behavior or type of behavior. The drug*genotype interaction was seen after one and two years of treatment and did not reverse one year after discontinuation of dosing. Two potential translational implications are suggested: (1) MAOA genetic polymorphisms may be the source of some of the variability in response to fluoxetine treatment in children; (2) extended fluoxetine treatment during juvenile brain development may result in persistent effects on emotional regulation.
authors.affiliation: University of California Davis, Department of Environmental Toxicology, Davis, California, USA. Electronic address: msgolub@ucdavis.edu.
authors.forename: M S
authors.initials: MS
authors.lastname: Golub
authors.affiliation: University of California Davis, California National Primate Research Center, Davis, California, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Hogrefe
authors.affiliation: University of California Davis, California National Primate Research Center, Davis, California, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Bulleri
mesh_terms: D000339:Affect / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004644:Emotions / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D005838:Genotype; D008253:Macaca mulatta; D008297:Male; D008995:Monoamine Oxidase / Q000187:drug effects* / Q000235:genetics; D010775:Photic Stimulation; D011110:Polymorphism, Genetic; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects
chemical_list: D005473:Fluoxetine; D008995:Monoamine Oxidase; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Behavior; Children; Emotion; Fluoxetine; MAOA; Nonhuman primates