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The regulation of liver cytochrome P450 expression and activity by the brain serotonergic system in different experimental models

ABSTRACT Introduction: Cytochrome P450 (CYP) metabolizes vital endogenous (steroids, vitamins) and exogenous (drugs, toxins) substrates. Studies of the last decade have revealed that the brain dopaminergic and noradrenergic systems are involved in the regulation of CYP. Recent research indicates that the brain serotonergic system is also engaged in its regulation. Areas covered: This review focuses on the role of the brain serotonergic system in the regulation of liver CYP expression. It shows the effect of lesion and activation of the serotonergic system after peripheral or intracerebral injections of neurotoxins, serotonin precursor, or serotonin (5-HT) receptor agonists. An opposite role of the hypothalamic paraventricular and arcuate nuclei and 5-HT receptors present therein in the regulation of CYP is described. The engagement of those nuclei in the neuroendocrine regulation of CYP by hypothalamic releasing or inhibiting hormones, pituitary hormones, and peripheral gland hormones are shown. Expert opinion: In general, the brain serotonergic system negatively regulates liver cytochrome P450. However, the effects of serotonergic agents on the enzyme expression depend on their mechanism of action, the route of administration (intracerebral/peripheral), as well as on local intracerebral site of injection and 5-HT receptor-subtypes present therein.