Altered Intracellular Signaling Associated with Dopamine D2 Receptor in the Prefrontal Cortex in Wistar Kyoto Rats

• Published in: International journal of molecular sciences 2023-03, Vol.24 (6), p.5941
• Main Authors: Korlatowicz, Agata, Kolasa, Magdalena, Pabian, Paulina, Solich, Joanna, Latocha, Katarzyna, Dziedzicka-Wasylewska, Marta, Faron-Górecka, Agata
• Format: Article
• Language: English
• Subjects: AKT protein; Animal models; Animals; Antidepressants; Autoradiography; beta Catenin - metabolism; Binding; Brain; Cardiac glycosides; Cardiotonic agents; Deep brain stimulation; Dopamine; dopamine D2 receptor; Dopamine D2 receptors; Drug resistance; G proteins; Gene expression; Genes; Glycogen; Glycogen synthase kinase 3; Glycogen Synthase Kinase 3 beta - genetics; Glycogen Synthase Kinase 3 beta - metabolism; Glycogens; Intracellular; intracellular signaling; Intracellular signalling; Kinases; Mental depression; mRNA; Neostriatum; Nucleus accumbens; Phenols; Phenotypes; Prefrontal cortex; Prefrontal Cortex - metabolism; Proteins; Rats; Rats, Inbred WKY; Rats, Wistar; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D2 - metabolism; Signal transduction; Stress; Stress response; Synthesis; Wistar-Kyoto rats; β-Catenin; βarrestin2/AKT/Gsk-3β/β-catenin pathway
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24065941

Wistar-Kyoto rats (WKY), compared to Wistar rats, are a well-validated animal model for drug-resistant depression. Thanks to this, they can provide information on the potential mechanisms of treatment-resistant depression. Since deep brain stimulation in the prefrontal cortex has been shown to produce rapid antidepressant effects in WKY rats, we focused our study on the prefrontal cortex. Using quantitative autoradiography, we observed a decrease in the binding of [ H] methylspiperone to the dopamine D2 receptor, specifically in that brain region-but not in the striatum, nor the nucleus accumbens-in WKY rats. Further, we focused our studies on the expression level of several components associated with canonical (G proteins), as well as non-canonical, D2-receptor-associated intracellular pathways (e.g., βarrestin2, glycogen synthase kinase 3 beta- , and β-catenin). As a result, we observed an increase in the expression of mRNA encoding the regulator of G protein signaling 2-RGS2 protein, which is responsible, among other things, for internalizing the D2 dopamine receptor. The increase in RGS2 expression may therefore account for the decreased binding of the radioligand to the D2 receptor. In addition, WKY rats are characterized by the altered signaling of genes associated with the dopamine D2 receptor and the βarrestin2/AKT/Gsk-3β/β-catenin pathway, which may account for certain behavioral traits of this strain and for the treatment-resistant phenotype.