The central mechanism of risperidone-induced hyperprolactinemia.
Risperidone is known to increase prolactin secretion in treating mental illness patients. This side-effect is thought to be mediated via central signaling pathway. However, the exact pathway involved between risperidone and hyperprolactinemia are still unknown. Therefore, we have treated mice with risperidone and investigated the central mechanisms. The present study showed that in risperidone treated group, the level of the serum prolactin significantly increased, which was consistent with increased positive prolactin staining in pituitary gland. Elevated c-fos expression was observed in the arcuate hypothalamic nucleus (Arc) where we found 65% c-fos positive neurons co-localised with neuropeptide Y (NPY) in mice treated with risperidone. In addition, the results from in situ hybridization showed that the NPY mRNA in the Arc was significantly increased, whereas the tyrosine hydroxylase (TH) mRNA dramatically decreased compared with control group in the paraventricular hypothalamic nucleus (PVN). These findings revealed that risperidone may mediate the transcriptional regulation of Arc NPY and TH in the PVN. Furthermore, risperidone induced a decreased dopamine synthesis in the PVN and thus reduced the dopamine-induced inhibition of prolactin release, ultimately lead to hyperprolactinemia. Therefore, insights into these neuronal mechanisms open up potential new ways to treat schizophrenia patients in order to ameliorate hyperprolactinemia.
Department of Cardiology, Southwest Hospital, Third Military Medical University, PR China.
Wei-Wei
WW
Sun
Department of Cardiology, Southwest Hospital, Third Military Medical University, PR China.
Lin-Yu
LY
Li
School of Medicine, Illawarra Health and Medical Research Institute, University of Wollongong, NSW 2522, Australia.
Xu-Feng
XF
Huang
Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
Yan-Chuan
YC
Shi
Department of Cardiology, Southwest Hospital, Third Military Medical University, PR China.
He-Qin
HQ
Yang
Department of Cardiology, Southwest Hospital, Third Military Medical University, PR China. Electronic address: zysong2010@126.com.
Zhi-Yuan
ZY
Song
Department of Cardiology, Southwest Hospital, Third Military Medical University, PR China; School of Medicine, Illawarra Health and Medical Research Institute, University of Wollongong, NSW 2522, Australia. Electronic address: shulin1956@126.com.
Shu
S
Lin
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D006966:Hyperprolactinemia / Q000097:blood / Q000139:chemically induced*; D008297:Male; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000187:drug effects*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D018967:Risperidone / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects*
D014150:Antipsychotic Agents; D009478:Neuropeptide Y; D014446:Tyrosine 3-Monooxygenase; D018967:Risperidone
Dopamine; Neural pathway; Neuropeptide Y; Prolactin; Risperidone