SERT models of emotional dysregulation

Abstract

ABSTRACT The serotonin system plays a key modulatory role in central nervous system processes that appear to be dysregulated in psychiatric disorders. Specifically, the serotonin transporter (SERT) is thought to be critical to many aspects of emotional dysregulation and has been a successful target for medications that treat several psychiatric disorders. Here, we narrowly focused on two psychiatric conditions; anxiety and depression, for which mice with SERT genetic manipulations have provided insight. Specifically, we suggest that dissecting syndromes according to a trait and state perspective may help us understand the complex and at times contradictory rodent results. The most compelling reason for this approach is provided by human studies, in which increased trait-neuroticism and stress-mediated vulnerability to develop depression were reported for subjects carrying the 5-HTTLPR s / s allele of the SERT gene, and thus placing the contribution of SERT to mood disorders in a gene × environment and trait/state context. Accordingly, current behavioral results in SERT knock-out (KO) mice are consistent with both increased trait and state anxiety-like behaviors, while evidence in support of a trait-based model of depression in SERT KO mice are inconsistent and mostly based on tests with limited relevance to human depression. However, comorbid symptoms associated with a wider definition of depression, such as altered gastrointestinal functions, lower pain threshold, and greater sensitivity to stress, have been reported in SERT KO mice, suggesting the presence of a pro-depressive state resulting from low SERT.