Selective Serotonin Reuptake Inhibitors (SSRIs) are the most commonly prescribed medications for the treatment of a range of behavioral and psychiatric disorders.While the clinical impact of SSRIs is well established,the genes and biochemical pathways underlying these disorders and molecular mechanisms of the therapeutic efficacy of the drugs remain unknown.In many neuronal circuits,serotonin functions as a neuromodulator facilitating and inhibiting synaptic transmission of other neurotransmitters,including acetylcholine,GABA and glutamate.The empirical action of SSRIs is blockade of the serotonin reuptake transporter (SERT) from removal of released serotonin at the synapse,thereby enhancing serotonin signaling.However,prevailing evidence suggests that SERT is not the only gene target of SSRIs.To experimentally elucidate the action of SSRIs on serotonin signaling pathways,ideally both the serotonergic system and drug efficacy should be amenable to genetic analysis.