Reversibility of dopamine receptor antagonist-induced hyperprolactinemia and associated histological changes in Tg RasH2 wild-type mice

Reproductive Toxicology
Gopala KrishnaSaryu Goel

Abstract

The purpose of this study was to better understand the biological effects of increased prolactin levels induced in mice by dopamine D2 receptor antagonist molindone treatment. Toxicokinetics, prolactin levels, and reproductive tissue histology were evaluated in Tg rasH2 wild-type mice treated orally with molindone at 0, 5, 15, and 50mg/kg/day for 6 months, followed by a 2-month posttreatment recovery period. A greater than dose-proportional increase in molindone exposure ([AUC]0‒24) was observed on Day 180 for both sexes. Statistically significant (P<0.01) increases in prolactin levels were observed in most treatment groups compared with controls at 0.5h postdose on Days 1 and 180. Prolactin levels returned to baseline levels during the recovery period. Microscopic changes attributable to hyperprolactinemia, including corpora lutea enlargement and interstitial cell atrophy in the ovaries, and atrophy of the uterus and vagina were observed on Day 180. These changes were reversed during the recovery period in the 5- and 15-mg/kg/day treatment groups. Mice receiving molindone at 50mg/kg/day also showed signs of reversal on histologic examination.

References

Jan 1, 1980·Journal of Pharmaceutical Sciences·J M Rosenberg, C A Lau-Cam
Mar 14, 2002·Toxicologic Pathology·Daniel MortonToshimi Usui
Nov 5, 2003·Biology of the Cell·Sophie CallierPhilippe Vernier
Apr 15, 2006·CNS & Neurological Disorders Drug Targets·T Kienast, A Heinz
Feb 20, 2007·Reproduction : the Official Journal of the Society for the Study of Fertility·Anne Bachelot, Nadine Binart
Jun 16, 2007·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Sabine RehmPatrick J Wier
Dec 7, 2007·Endocrine Reviews·Nira Ben-JonathanElizabeth W LaPensee
Apr 29, 2008·Toxicologic Pathology·F Russell Westwood
May 25, 2010·Journal of the American Academy of Child and Adolescent Psychiatry·Robert L FindlingLinmarie Sikich
Aug 17, 2010·Regulatory Toxicology and Pharmacology : RTP·Takeshi KunimatsuTakaki Seki
Aug 25, 2010·Reproduction : the Official Journal of the Society for the Study of Fertility·Marcel EgliTillmann H C Kruger
Oct 16, 2014·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Shelley S TworogerSusan E Hankinson

❮ Previous
Next ❯

Citations

Sep 28, 2017·Cancer Biomarkers : Section a of Disease Markers·Suxian LuanLiangzhi Sun
Sep 20, 2018·Birth Defects Research·Gopakumar GopalakrishnanChungping Yu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antipsychotic Drugs

Antipsychotic drugs are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. Discover the latest research on antipsychotic drugs here

Attention Disorders

Attention is involved in all cognitive activities, and attention disorders are reported in patients with various neurological diseases. Here are the latest discoveries pertaining to attention disorders.

Cardiomegaly

Cardiomegaly, known as an enlarged heart, is a multifactorial disease with different pathophysiological mechanisms. Hypertension, pregnancy, exercise-induced and idiopathic causes are some mechanisms of cardiomegaly. Discover the latest research of cardiomegaly here.