The central mechanism of risperidone-induced hyperprolactinemia

Area of Science:

• Neuroscience
• Endocrinology
• Pharmacology

Background:

• Risperidone, an antipsychotic, is known to increase prolactin secretion.
• The central signaling pathways mediating risperidone-induced hyperprolactinemia remain unclear.
• Understanding these mechanisms is crucial for managing side effects in mental illness patients.

Purpose of the Study:

• To investigate the central neuronal mechanisms underlying risperidone-induced hyperprolactinemia in mice.
• To elucidate the specific hypothalamic nuclei and neurotransmitters involved in this side effect.

Main Methods:

• Mice were treated with risperidone.
• Serum prolactin levels and pituitary prolactin staining were measured.
• Expression of c-fos, neuropeptide Y (NPY), and tyrosine hydroxylase (TH) mRNA in hypothalamic nuclei (Arcuate Nucleus and Paraventricular Nucleus) were analyzed using immunohistochemistry and in situ hybridization.

Main Results:

• Risperidone significantly increased serum prolactin and pituitary prolactin staining.
• Elevated c-fos expression was observed in the arcuate nucleus (Arc), with 65% co-localization with NPY.
• NPY mRNA in the Arc increased, while tyrosine hydroxylase (TH) mRNA in the paraventricular nucleus (PVN) decreased.
• Dopamine synthesis in the PVN was reduced.

Conclusions:

• Risperidone induces hyperprolactinemia by altering NPY and TH expression in the hypothalamus.
• The drug decreases dopamine synthesis in the PVN, reducing dopamine's inhibitory effect on prolactin release.
• These findings provide novel insights into potential therapeutic strategies for managing risperidone-induced hyperprolactinemia in schizophrenia patients.