The regulation of SKF38393 on the signaling pathway of dopamine D1 receptor in hippocampus during chronic sleep deprivation

Background: Hippocampal functions are sensitive to sleep deficiency. Dopamine D1 receptor (D1R) in hippocampus can regulate the expression of cAMP response element binding protein (CREB) through PICA, MAPK and phosphoinositide pathway, but which pathway plays the major role in hippocampus during Chronic sleep deprivation (CSD) is unclear. Methods: The CSD model was created, SKF rats were administered the D1R agonist (SKF38363), and hippocampus from each animal was dissected for following molecular detection. The gene and protein levels of CREB and key molecules in D1R pathways were measured by real-time PCR and western blotting, respectively. Results: Both the gene and protein expression of CREB in hippocampus decreased by CSD and improved significantly by SKF38393 (p <0.05). Both the gene and protein expression of PICA in hippocampus decreased by CSD and improved significantly by SKF38393 (p <0.05). SKF38393 just significantly improved the gene level of CaMK IV and the protein level of p-CaMIC IV (p <0.05) in CSD rats, but it cannot improve the protein expression of ERK1/2 and p-ERK1/2. Discussion: CSD significantly decreased the expression of CREB in hippocampus. As the key molecules, PICA and CaMK IV play an important role during the improvement of hippocampus by the activation of D1R, and this process might be improved during CSD through the PICA and phosphoinositide pathway. (C) 2017 Elsevier B.V. All rights reserved.