<p>Synthetic glucocorticoids, such as dexamethasone, 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 dexamethasone (8&#xa0;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 and real-time quantitative reverse transcription polymerase chain reaction. We found that dexamethasone exerts a pronounced, region-specific impact on neurotransmitter systems. In the striatum, dexamethasone increased dopamine and serotonin levels while simultaneously reducing their catabolism, which was associated with decreased messenger ribonucleic acid expression of monoamine oxidase A, monoamine oxidase B, tryptophan hydroxylase and increased expression of tyrosine hydroxylase. In the hippocampus, dexamethasone elevated serotonin levels and reduced its turnover despite an increase in monoamine oxidase A messenger ribonucleic acid expression, suggesting the potential involvement of post-transcriptional regulation or alternative metabolic pathways. In the prefrontal cortex, dexamethasone induced a reduction in norepinephrine levels, accompanied by a decrease in monoamine oxidase A and catechol-O-methyltransferase messenger ribonucleic acid expression. This study highlights the importance of considering region-specific cerebral effects of glucocorticoids for the development of personalized therapeutic and neuroprotective strategies, including the potential use of dexamethasone in conditions such as Parkinson’s disease due to its ability to elevate striatal dopamine levels.</p>