Experimental Models in Serotonin Transporter Research.

Serotonin is a neurotransmitter involved in emotional regulation and nervous system development. The most commonly prescribed antidepressants are the selective serotonin reuptake inhibitors (SSRIs) that target the serotonin transporter (SERT). In human populations, the SERT gene has a promoter region polymorphism that controls SERT expression level. The short allele is associated with lower SERT level, anxiety-like traits, and depression, making this gene of great interest in behavioral neurogenetics. In Experimental Models in Serotonin Transporter Research, a team of experts from diverse backgrounds critically review the most recent research on SERT and its clinical relevance. The first two chapters are a useful review of the current efforts to understand the cellular and molecular mechanisms underlying SERT phenotypes in rodents. Unfortunately, a range of dosages, delivery methods, and different durations and timings of treatment frequently generate conflicting results. Constitutive and chronic disruption of SERT is contrasted with perturbations administered in adulthood. Chapter 3 specifically addresses the developmental, or “structural,” role of serotonin and SERT, which is a fascinating field in itself and provides critical background for interpreting chronic perturbations to the serotonin system. The subsequent chapters review the use of SERT mutant rodents to model depression and anxiety. Rodents are invaluable for understanding the interplay between genetics, environment, and behavior as they can be genetically manipulated and studied in a controlled environment. SERT knockout and knockdown mice have been studied extensively using a variety of behavioral testing paradigms and biological markers thought to correspond to human symptoms. Two approaches to modeling serotonin function in rats are presented: a SERT knockout line and lines selectively bred for high and low platelet serotonin levels. Curiously, both groups of rats differ noticeably from their wild-type counterparts only when confronted with an environmental or pharmacological challenge. The book then goes on to describe the interaction between the serotonin system and other neurotransmitters, particularly dopamine, in models of drug reward. Primates, like humans, have complex social lives yet can be reared under controlled conditions and subjected to behavioral experiments. Simian primates possess a promoter polymorphism similar to humans and also show comparable behavioral traits. Chapters 10 and 11 are a fascinating discussion of the serotonin system in human and primate social behavior. The interaction between genes and the environment emerges as a central theme in neural development with alleles conferring differential sensitivity to adverse life experiences. Importantly, variation in SERT expression could predispose individuals to psychiatric disorders and, more generally, contribute to inter-individual personality differences. This volume will be of greatest interest to specialists, both basic scientists and clinicians, but the relevance of the serotonin system to various aspects of human behavior may make it a useful reference for curious outsiders. In such complex fields where a great diversity of models and experimental methods are used, a collection of expert reviews should be of great value in making sense of the complicated and sometimes conflicting results.