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Unraveling mechanisms contributing to lack of antidepressant efficacy in juveniles and adolescents
Author(s) -
Mitchell Nathan Clark,
Horton Rebbeca E.,
Vitela Melissa,
Gould Georgianna G.,
Koek Wounter,
Daws Lynette C.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1099.1
Subject(s) - antidepressant , monoamine neurotransmitter , serotonin , serotonin transporter , depression (economics) , pharmacology , fluoxetine , juvenile , norepinephrine , medicine , psychiatry , psychology , biology , dopamine , receptor , genetics , macroeconomics , economics , anxiety
Depression is a major health problem for which most patients are not effectively treated. This problem is further compounded in children and adolescents where only two antidepressants [both selective serotonin reuptake inhibitors (SSRIs)] are currently approved for clinical use. Mouse models provide tools to identify mechanisms that might account for poor treatment response to antidepressants. However, until now the use of such models has been limited to studies in adult mice. Here we show that the tail suspension test can be used to assay antidepressant‐like effects of reference drugs in mice aged 21 (juvenile) and 28 (adolescent) days post‐partum, and that the antidepressant‐like activity of these drugs relates positively to expression levels of serotonin‐ and norepinephrine transporters. Importantly, we found that juvenile mice had markedly greater expression levels of plasma‐membrane monoamine transporter (PMAT) than adult mice. PMAT clears serotonin from extracellular fluid, and therefore may limit the therapeutic efficacy of SSRIs, providing a mechanistic basis for poor treatment response to SSRIs, particularly in juveniles and adolescents.