title: Elevated dopamine D2 receptor in prefrontal cortex of CUMS rats is associated with downregulated cAMP-independent signaling pathway.
abstract: Because depression is associated with significant morbidity and functional disability, it is important to reveal the mechanism of action. A variety of studies have suggested the involvement of dopaminergic receptors in the pathophysiological mechanism of non-stress-associated depression-like behavior in rodents. Nevertheless, controversy exists about whether chronic stress acts on dopaminergic receptors in the prefrontal cortex. Thus, we investigated the level of dopamine D2 receptors (DRD2) and the possible mechanisms involved in a chronic unpredictable mild stress (CUMS) rat model of depression. The results showed CUMS-induced, depression-like symptoms in the rat, characterized by reduced sucrose consumption and body mass, and increased duration of immobility in a forced swimming test. Moreover, chronic stress upregulated the expression of DRD2 but downregulated protein kinase A (PKA), transcription factor cAMP response element binding protein (CREB), and phospho-CREB (p-CREB) in the prefrontal cortex, as demonstrated by Western blot. Notably, in the rat model of depression, decreased cyclic adenine monophosphate (cAMP) levels and PKA activity were present at the same time, which is consistent with clinical findings in depressed patients. Our findings suggested that dopaminergic system dysfunction could play a central role in stress-related disorders such as depression.
authors.affiliation: Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry, Hefei 230032, Anhui, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Jing-mo
authors.initials: JM
authors.lastname: Yang
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Hu
authors.forename: Ting-juan
authors.initials: TJ
authors.lastname: Xu
authors.forename: Wei-ping
authors.initials: WP
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003863:Depression / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D005518:Food Preferences; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015398:Signal Transduction; D013315:Stress, Psychological / Q000150:complications*; D013550:Swimming; D013997:Time Factors; D015854:Up-Regulation; D015431:Weight Loss
chemical_list: C508137:Creb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D019422:Dietary Sucrose; D017448:Receptors, Dopamine D2; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs