Elevated dopamine D2 receptor in prefrontal cortex of CUMS rats is associated with downregulated cAMP-independent signaling pathway.

Publisher: Canadian Science Publishing Country of Publication: Canada NLM ID: 0372712 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1205-7541 (Electronic) Linking ISSN: 00084212 NLM ISO Abbreviation: Can J Physiol Pharmacol Subsets: MEDLINE

Publication: 2011- : Ottawa, ON : Canadian Science Publishing
Original Publication: Ottawa, National Research Council of Canada.

Signal Transduction*; Cyclic AMP/*metabolism ; Depression/*metabolism ; Prefrontal Cortex/*metabolism ; Receptors, Dopamine D2/*metabolism ; Stress, Psychological/*complications; Animals ; Behavior, Animal ; Blotting, Western ; Cyclic AMP Response Element-Binding Protein/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Depression/etiology ; Depression/physiopathology ; Depression/psychology ; Dietary Sucrose/administration & dosage ; Disease Models, Animal ; Food Preferences ; GTP-Binding Protein alpha Subunits, Gi-Go/metabolism ; GTP-Binding Protein alpha Subunits, Gs/metabolism ; Immunohistochemistry ; Male ; Motor Activity ; Phosphorylation ; Prefrontal Cortex/physiopathology ; Rats ; Rats, Sprague-Dawley ; Swimming ; Time Factors ; Up-Regulation ; Weight Loss

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.

0 (Creb1 protein, rat)
0 (Cyclic AMP Response Element-Binding Protein)
0 (Dietary Sucrose)
0 (Receptors, Dopamine D2)
E0399OZS9N (Cyclic AMP)
EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)

Date Created: 20130830 Date Completed: 20140321 Latest Revision: 20231213

20240829

10.1139/cjpp-2012-0399

23984873