thus lowering the efficiency with which serotonin signaling can occur across the synapse. these findings suggest that, although the serotonin levels are immediately introduced via medication, the period of time within which the medicine alleviates the patient's depression most likely relies on other regulatory proteins. thus, given protein p11's interaction with serotonin 5-ht receptors and the increasing evidence of the protein's correlation to mood disorders, this protein has been identified as a target for research in the development of future antidepressants. treatment with antidepressants (a tricyclic and monoamine oxidase inhibitor) and electroconvulsive therapy (ect) caused an increase in the amount of p11 in the brain of these mice - the same biochemical change. the levels of the p11 protein in humans and mice with symptoms of depression were substantially lower in comparison to the levels of p11 in non-depressed animals. leading researcher paul greengard and his colleagues hypothesized that increasing p11 levels would result in the mice exhibiting antidepressant-like behaviors, and the opposite if p11 protein levels were reduced. they used a test that is used to measure antidepressant-like activity to affirm this hypothesis. in their findings, over-expressed p11 genes, compared to the control mice, had increased mobility and more 5-ht1b receptors at the cell surface, which made possible more serotonin transmission. when researchers "knocked out" the p11 gene in mice, they found that the knockout mice had fewer receptors at the cell surface, reduced serotonin signaling, reduced responsiveness to sweet reward, and decreased mobility, behaviors all characteristic of depression-like behaviors. also, the 5-ht1b receptors of p11 knockout mice were less responsive to serotonin and antidepressant drugs compared to those of control mice, which further implicates p11 in the main action of antidepressant medications. antidepressant manipulations increase the p11 levels, whereas depressant manipulations reduce it. therefore, in order to achieve an anti-depression effect, antidepressant medications should focus on the main action of the p11 proteins and increase levels of the protein. future clinical trials at the current time, a study by the national institutes of health clinical center (cc) is recruiting participants for a study that will compare levels of p11 protein in people with and without major depressive disorder (mdd) and determine whether p11 levels in patients are affected by treatment with citalopram (celexa), a serotonin reuptake inhibitor. if successful, a more personalized treatment of mdd will be available in the future.