Ethinyl Estadiol/Progestin Oral Contraceptives Depress Spatial Learning and Dysregulate Hippocampal CA3 Microstructure: Implications for Behavioral-Cognitive Effects of Chronic Contraceptive Use?

Abstract

Abstract Combined oral contraceptive pill contains ethinyl estradiol and a synthetic progestin, which prevent ovulation by suppressing the release of the gonadotropins resulting in the inhibition of ovarian follicles’ development. Although advantageous in birth control, the impact on learning and memory is limited necessitating this study on its effect on spatial learning, and hippocampal CA3 microstructure. Thirty two female Wistar rats of average body weight 200 g were equally divided (n = 8) into four groups; 0.002 mg/kg levonorgestrel plus 0.00043 mg/kg ethinyl estradiol (COCP) were administered orally for 21, 42 and 63 days. 24 hours after the last administration the rats underwent Morris water maze test and were sacrificed by transcardial perfusion-fixation. Their hippocampal regions were processed for histological study, and immunolabelled with anti-neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP). Results showed that the COCP test groups had shorter escape latencies (p ≤ 0.05) in the visible and hidden platform trials. The COCP test groups showed no difference in neuronal population, although some of the hippocampal CA3 pyramidal neurons were either atrophic and/or karyorrhectic, with shrunken and dense nuclei. NSE expression was lower (p ≤ 0.05) in the 21, 42 and 63 days COCP groups, while GFAP expression was lower in the 21 days COCP group, but not different in the 42 and 63 days COCP groups compared with the control. These preliminary results show that COCP influence spatial learning, and may also reduce neuronal metabolic activity, while increasing astrocytic activity in the hippocampal CA3.