Treatment of mice or rats with serotonin reuptake inhibiting antidepressants (SRIs) during a specific period shortly after birth results in increased anxiety- and depressive-like behavior in adulthood. Here, we will extend our studies on the use of voltammetry methods to investigate the role of the serotonin transporter (SERT) in anxiety and depression to include this important model of postnatal inhibition of serotonin reuptake. We will use chronoamperometry to determine changes in serotonin uptake rates during periadolescence and adulthood arising from postnatal treatment with an SRI. We have demonstrated previously that the use of high-speed chronoamperometry to measure serotonin uptake in brain synaptosomes is superior to traditional radiochemical methods. We will also utilize quantitative autoradiography to evaluate changes in serotonin transporter binding sites to determine whether alterations in SERT function and expression are correlated. There is recent evidence that hippocampal SERT function and expression increase during early and middle adult periods in normal animals. The design of this study will allow us to investigate whether this developmental trajectory begins prior to adulthood. We will also determine whether it is present in brain regions other than hippocampus that are innervated by the serotonergic system and are important for modulating anxiety and mood. Moreover, we will test the hypothesis that postnatal administration of SRIs disrupts normal periadolescent and adult development of SERT function and expression. The results of this study will allow us to interpret whether alterations in normal SERT development occurring during adolescent and/or adult time frames are key elements contributing to the altered phenotype induced by postnatal SRI exposure. This has ramifications for our understanding of normal development of the serotonergic system and for altered trajectories related to early life exposure to SRIs.
Treatment of mice or rats with serotonin reuptake inhibiting antidepressants for a short period after birth leads to elevated anxiety and depressive behavior in adulthood. We will use a state-of-the-art electrochemical method to determine whether reductions in serotonin reuptake persist long after the cessation of drug treatment. We will explore the idea that early life exposure to antidepressants alters the normal development of serotonin transporter function and expression. The results of this study will increase our understanding of normal brain development and altered developmental trajectories related to early life exposure to antidepressants.
|Yang, Hongyan; Sampson, Maureen M; Senturk, Damla et al. (2015) Sex- and SERT-mediated differences in stimulated serotonin revealed by fast microdialysis. ACS Chem Neurosci 6:1487-501|
|Altieri, Stefanie C; Yang, Hongyan; O'Brien, Hannah J et al. (2015) Perinatal vs genetic programming of serotonin states associated with anxiety. Neuropsychopharmacology 40:1456-70|
|Stein, Murray B; Andrews, Anne M (2015) Serotonin States and Social Anxiety. JAMA Psychiatry 72:845-7|