Immunohistochemical Changes after Metoclopramide Administration in Rat Brain Cells

Abstract

Metoclopramide, used as an anti-emetic drug in clinical practice, has recently also begun being used to establish hyperprolactinemic effects in the breastfeeding. The purpose of this study was to investigate the potential side-effects of metoclopramide applied in the lactation period in the central nervous system of infant rats. 18 female albino Wistar rats that had just given birth were divided into 3 groups together with their pups: Healthy controls, low-dose metoclopramide (10 mg/kg, twice per day i.p.) and a high-dose metoclopramide group (45 mg/kg, twice per day i.p.). Brain tissues from 6 pups from each mother were harvested at the end of the 21st day. Immunohistochemical technique was performed using dopamine D2 receptor (DRD2), brain derived neurotrophic factor (BDNF) and neural growth factor (NGF), markers of extrapyramidal reaction in the brain, as signal molecules. Based on immunohistochemical results, DRD2 expression decreased only in the external pyramidal layer neurons in the high-dose infant group. Strong BDNF reaction was determined in pyramidal neurons in all layers in the control infant group, and decreased reaction was observed in the high- and low-dose groups. No significant difference was observed in NGF expression between the three groups. Since high-dose metoclopramide caused a decrease in DRD2 expression in the external pyramidal layer in the prefrontal cortex, and since both high and low doses reduced BDNF expression, care needs to be taken with the use of metoclopramide in the lactation period due to the possibility of extrapyramidal reactions in infants.

Keywords

• brain
• extrapyramidal reactions
• metoclopramide