title: Minocycline produced antidepressant-like effects on the learned helplessness rats with alterations in levels of monoamine in the amygdala and no changes in BDNF levels in the hippocampus at baseline.
abstract: Previous studies have indicated that minocycline might function as an antidepressant drug. The aim of this study was to evaluate the antidepressant-like effects of minocycline, which is known to suppress activated microglia, using learned helplessness (LH) rats (an animal model of depression). Infusion of minocycline into the cerebral ventricle of LH rats induced antidepressant-like effects. However, infusion of minocycline into the cerebral ventricle of naïve rats did not produce locomotor activation in the open field tests, suggesting that the antidepressant-like effects of minocycline were not attributed to the enhanced locomotion. LH rats showed significantly higher serotonin turnover in the orbitofrontal cortex and lower levels of brain-derived neurotrophic factor (BDNF) in the hippocampus than control rats. However, these alterations in serotonin turnover and BDNF expression remained unchanged after treatment with minocycline. On the contrary, minocycline treatment of LH rats induced significant increases in the levels of dopamine and its metabolites in the amygdala when compared with untreated LH rats. Taken together, minocycline may be a therapeutic drug for the treatment of depression.
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Arakawa
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Shirayama
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Tamaki
authors.initials: T
authors.lastname: Ishima
authors.forename: Mao
authors.initials: M
authors.lastname: Horio
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Muneoka
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001362:Avoidance Learning; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006380:Helplessness, Learned; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D057967:Infusions, Intraventricular; D008297:Male; D008911:Minocycline / Q000008:administration & dosage / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D019208:Brain-Derived Neurotrophic Factor; D012701:Serotonin; D008911:Minocycline; D004298:Dopamine