Candidate Review:

Getting beyond Prozac: A C. elegans approach

Leda Ramoz

Neuroscience Graduate Program, Vanderbilt University School of Medicine, U1205 Medical Center North, Nashville, TN 37232, USA.
Correspondence e-mail: leda.ramoz@vanderbilt.edu

Abstract | Full Text | PDF

Abstract | Since its debut in 1986 the selective serotonin reuptake inhibitor (SSRI) fluoxetine (ProzacTM) has taken society and mental illness by storm, becoming one of the most widely prescribed medications in America for the treatment of depression, obsessive-compulsive-disorder, bulimia nervosa, and anxiety1. Despite its pervasiveness in society, the exact mechanism of action of these and other antidepressants as well as their effects on endogenous regulation of their target protein, the serotonin transporter2 are largely unknown. Synaptic serotonergic activity is primarily regulated by recycling of (5-hydroxytryptamine, 5-HT) from the synaptic cleft through activity of the presynaptic serotonin transporter (SERT, 5-HTT, SLC6A4)3, 4, a transmembrane protein that is a major target of psychostimulants such as MDMA (“ecstasy”) as well as many antidepressants such as fluoxetine5,2. The monoamine neurotransmitter 5-HT is an important modulator of vertebrate cardiovascular and cognitive function regulating a wide range of physiological and behavioral processes including gut function, body temperature, sleep, appetite, aggression, and mood6. SERT deregulation is linked to a variety of disease states, those listed above as well as alcoholism and autism1,7-9, yet we are only beginning to understand the mechanisms behind endogenous regulation of SERT.