Experimental Models in Serotonin Transporter Research: The serotonin transporter and animal models of depression

ABSTRACT The serotonin transporter (SERT), a membrane protein responsible for the reuptake of extracellular serotonin, is a prominent target of antidepressants. Moreover, a polymorphism of this gene that decreases serotonin uptake has been linked to depression. However, the role of SERT in depression is poorly understood. Several functional impairments, notably in behavior, sleep, and response to stress, are consistently found in animal models of depression, but consistent correlation with serotonergic dysfunction has not been demonstrated. Nevertheless, in certain genetic backgrounds, the same impairments are also found in mutant rodents in which serotonin transport has been abolished. These impairments are also observed in adult rodents after a transient disruption of serotonin transport during the first postnatal month. Conversely, they may be prevented in mutant rodents by normalizing serotonergic transmission postnatally. Therefore, the function of the serotonin transporter during postnatal development is critical for the proper maturation of brain circuits, while susceptibility to depression caused by reduced serotonin transporter function may be determined, in part, during development. INTRODUCTION Depression is one of the most common psychiatric disorders in developed countries. This disease affects mood, psychomotor activity, neurovegetative functions, and cognition (Fava and Kendler,2000). Estimates indicate a lifetime prevalence up to 20% for major depression (Blazer, 2000; Fava and Kendler, 2000; Kornstein et al ., 2000), and the likelihood of experiencing this disorder is twice as high in women as in men (Kornstein et al ., 2000). Depression can be a lifelong episodic disorder with multiple recurrences.