Sulpiride-Induced Hyperprolactinemia in Mature Female Rats: Evidence for Alterations in The Reproductive System, Pituitary and Ovarian Hormones

Background: The prevalence of hyperprolactinemia following administration of conventional antipsychotic drugs requires further investigation. The current study is designed to evaluate the effect of sulpiride (SPD)-induced hyperprolactinemia on alterations to ovarian follicular growth, gonadotropins, and ovarian hormones and to analyze the extent of potential problems in mammary glands. Materials and Methods: A total of 40 albino Wistar rats were divided into four groups: control (no treatment), control-sham (0.3 ml olive oil), low dose SPD (20 mg/kg) and high dose SPD (40 mg/kg). All compounds were intraperitoneally (IP) administered for a period of 28 days. Results: After 28 days, we dissected the rats’ ovarian tissues, uterine horns and mammary glands which were sent for histological analyses. We counted the numbers of normal, atretic follicles and corpora lutea (CL). Serum levels of prolactin (PRL), estradiol, progesterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were evaluated. SPD-administered animals showed sporadic follicular atresia in different sizes associated with higher numbers of CL on the ovaries. The mammary glands exhibited features of galactorrhea. There was remarkable (p < 0.05) elevation in SPD-administered animals’ uterine horn endometrium, myometrium and perimetrium thicknesses. The serum levels of PRL and progesterone significantly (p < 0.05) increased, while the serum concentration of estradiol, LH and FSH notably (p < 0.05) decreased according to the SPD administered dose. No histological and biological changes occurred in control-sham animals. SPD-induced animals had unsuccessful attempts at mating and decreased pregnancy rates. Conclusion: The present findings suggest that SPD-induced disturbances depend on PRL level. In addition, an increased PRL level is largely dependent on the administered doses of SPD.