title: Burst-firing patterns in the prefrontal cortex underlying the neuronal mechanisms of depression probed by antidepressants.
abstract: Major depressive disorder (MDD) is one of the leading causes of morbidity worldwide. Several antidepressants have been widely prescribed to treat patients with MDD. However, neuronal changes in brain function remain poorly understood. Based on the standard chronic mild stress (CMS) model of depression in mice, we investigated the neuronal mechanisms of the classic antidepressant, fluoxetine, and a new compound (termed YY-23 in this study) derived from furostanol saponin. The results showed that both fluoxetine and YY-23 normalized CMS-induced depressive-like behaviors. YY-23 caused antidepressant-like behaviors with a faster action than fluoxetine. In terms of in vivo neuronal activities, a CMS-induced decrease in spontaneous firing in burst of medial prefrontal cortex pyramidal neurons rather than ventral tegmental area (VTA) was reversed by the chronic administration of fluoxetine and YY-23. We also found that CMS-induced deficits in the expression of prefrontal brain-derived neurotrophic factor (BDNF) were also restored by chronically administering YY-23 and fluoxetine. In addition, chronic administration of fluoxetine rather than YY-23 resulted in an improvement of antidepressive-like behavior and a change of burst firing of VTA in control-housed animals, indicating that the pharmacological effects of YY-23 were specific to CMS-treated animals. Together, these data suggest that the burst-firing patterns of pyramidal cells may be a neural biomarker of depressive-like mice and antidepressant action. Furthermore, synaptic transmission and BDNF may contribute to the rapid antidepressant-like effects on depression.
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medical, Chinese Academy of Sciences, Shanghai, 201203, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Fu
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Chenggang
authors.initials: C
authors.lastname: Huang
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002908:Chronic Disease; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D051379:Mice; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000503:physiopathology; D011897:Random Allocation; D013315:Stress, Psychological; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D005473:Fluoxetine
keywords: brain-derived neurotrophic factor; medial prefrontal cortex; mouse; ventral tegmental area