title: PI3K/Akt signaling pathway in the basolateral amygdala mediates the rapid antidepressant-like effects of trefoil factor 3.
abstract: Depression is one of the most common and debilitating psychiatric illnesses around the world, but the current antidepressants used to treat depression have many limitations. Progressively more studies have shown that neuropeptide systems are potential novel therapeutic targets for depression. However, whether the neuropeptide trefoil factor 3 (TFF3) participates in the development of depression has not been examined. In the current experiments, we assessed the antidepressant effects of TFF3 using the forced swim test (FST), tail suspension test (TST), and chronic mild stress (CMS) paradigm. Furthermore, we determined the mechanism that underlies the antidepressant-like effects of TFF3 in the rat FST. TFF3 dose-dependently reduced immobility time in both FST and TST. CMS elevated plasma TFF3 and decreased basolateral amygdala (BLA) TFF3 levels in rats, and acute TFF3 (0.1 mg/kg, i.p.) treatment reversed the depressive-like behaviors induced by CMS. Furthermore, TFF3 (0.1 mg/kg, i.p.) significantly increased Fos expression in the BLA, medial prefrontal cortex, and hypothalamus in rats subjected to the FST. Intra-BLA infusions of TFF3 (1 ng/side) exerted rapid antidepressant-like effects in the rat FST. Additionally, acute systemic TFF3 administration increased the level of phosphorylated-Akt (p-Akt) in the BLA. Finally, intra-BLA infusions of LY294002 (5 mM/side), a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, significantly blocked the antidepressant-like effect of TFF3. Our results demonstrated that TFF3 exerts antidepressant-like effects that might be mediated by the PI3K/Akt signaling pathway in the BLA. These findings suggest a novel neuropeptide system target in the development of new antidepressants.
authors: National Institute on Drug Dependence, Peking University, Beijing, China.
authors: Hai-Shui
authors: HS
authors: Shi
authors: Wei-Li
authors: WL
authors: Zhu
authors: Jian-Feng
authors: JF
authors: Liu
authors: Yi-Xiao
authors: YX
authors: Luo
authors: Ji-Jian
authors: JJ
authors: Si
authors: Shen-Jun
authors: SJ
authors: Wang
authors: Yan-Xue
authors: YX
authors: Xue
authors: Zeng-Bo
authors: ZB
authors: Ding
authors: Jie
authors: J
authors: Shi
authors: Lin
authors: L
authors: Lu
mesh_terms: D000208:Acute Disease; D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D000928:Antidepressive Agents; D015153:Blotting, Western; D002908:Chronic Disease; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D019417:Hindlimb Suspension / Q000523:psychology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000502:physiology*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013315:Stress, Psychological / Q000523:psychology; D013550:Swimming / Q000523:psychology; D000071165:Trefoil Factor-3
chemical_list: D000928:Antidepressive Agents; D051058:Oncogene Protein v-akt; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011994:Recombinant Proteins; D000071165:Trefoil Factor-3; C082495:TFF3 protein, human