Single Intraperitoneal Injection of Dexamethasone Alerts Region-specific Neurotransmitter Metabolism in Rat Brain

Synthetic glucocorticoids (GCs), such as dexamethasone (DEX), are widely used in therapy; however, their administration at high doses may be associated with effects on the central nervous system, particularly on neurotransmitter systems, yet the molecular mechanisms underlying these phenomena remain poorly understood. In this study, we investigated the effects of a single intraperitoneal administration of DEX (8 mg/kg) on the metabolism of key monoamines and the expression of their metabolic enzymes in various rat brain regions (striatum, hippocampus, and prefrontal cortex) using high-performance liquid chromatography (HPLC) and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). We found that DEX exerts a pronounced, region-specific impact on neurotransmitter systems. In the striatum, DEX increased dopamine (DA) and serotonin (5-HT) levels while simultaneously reducing their catabolism, which was associated with decreased messenger ribonucleic acid (mRNA) expression of monoamine oxidase A (MAOA) and monoamine oxidase B (MAOB) and increased expression of tyrosine 3‑monooxygenase (TH). In the hippocampus, DEX elevated serotonin levels and reduced its turnover despite an increase in MAOA mRNA expression, suggesting the potential involvement of post-transcriptional regulation or minor metabolic enzymes. In the cortex, DEX induced a two-fold reduction in norepinephrine (NE) and its metabolite, as well as a decrease in MAOA and COMT mRNA expression. This study highlights the importance of considering region-specific cerebral effects of GCs for the development of personalized therapeutic and neuroprotective strategies, including the potential use of DEX in conditions such as Parkinson’s disease due to its ability to elevate striatal DA levels.