Ketamine enhances dopamine D1 receptor expression by modulating microRNAs in a ketamine-induced schizophrenia-like mouse model.
Neurotoxicology and Teratology February 21, 2022 Xiaojiaoyang Li, Juanhan Yu, Xue Wu et al.
High-dose ketamine given to mice for seven consecutive days produced schizophrenia-like symptoms, including increased activity and impaired spatial learning and memory. Ketamine reduced levels of three microRNAs (miR-15a-3p, miR-15b-3p, miR-16-1-3p) in the prefrontal cortex and one (miR-16-1-3p) in the hippocampus, while increasing expression of the dopamine D1 receptor (DRD1) in those brain regions. In mouse hippocampal neurons, ketamine raised DRD1 levels in a dose-dependent way, and adding mimics of miR-15b-3p and miR-16-1-3p partially reversed this increase. A specific sequence in the DRD1 gene's regulatory region was identified as the target of these microRNAs.