title: SERT and uncertainty: serotonin transporter expression influences information processing biases for ambiguous aversive cues in mice.
abstract: The long allele variant of the serotonin transporter (SERT, 5-HTT) gene-linked polymorphic region (5-HTTLPR) is associated with higher levels of 5-HTT expression and reduced risk of developing affective disorders. However, little is known about the mechanisms underlying this protective effect. One hypothesis is that 5-HTT expression influences aversive information processing, with reduced negative cognitive bias present in those with higher 5-HTT expression. Here we investigated this hypothesis using genetically-modified mice and a novel aversive learning paradigm. Mice with high levels of 5-HTT expression (5-HTT over-expressing, 5-HTTOE mice) and wild-type mice were trained to discriminate between three distinct auditory cues: one cue predicted footshock on all trials (CS+); a second cue predicted the absence of footshock (CS-); and a third cue predicted footshock on 20% of trials (CS20%), and was therefore ambiguous. Wild-type mice exhibited equivalently high levels of fear to the CS+ and CS20% and minimal fear to the CS-. In contrast, 5-HTTOE mice exhibited high levels of fear to the CS+ but minimal fear to the CS- and the CS20%. This selective reduction in fear to ambiguous aversive cues suggests that increased 5-HTT expression reduces negative cognitive bias for stimuli with uncertain outcomes.
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford, UK.
authors.forename: S B
authors.initials: SB
authors.lastname: McHugh
authors.forename: C
authors.initials: C
authors.lastname: Barkus
authors.forename: J
authors.initials: J
authors.lastname: Lima
authors.forename: L R
authors.initials: LR
authors.lastname: Glover
authors.forename: T
authors.initials: T
authors.lastname: Sharp
authors.forename: D M
authors.initials: DM
authors.lastname: Bannerman
mesh_terms: D000818:Animals; D003214:Conditioning, Classical; D003463:Cues; D004192:Discrimination, Psychological; D005239:Fear; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse
keywords: 5-HTT; 5-HTTLPR; SERT; ambiguous; animal model; cognitive bias; fear; mice; over-expressing; serotonin transporter
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