Effect of neonatal administration of the opioid peptide dalargin on long-term cerebral consequences of antenatal hypoxia

Abstract

The aim of the study was to analyze the effect of δ/μ-agonist dalargin (Tyr-D-Ala-Gly-Phe-Leu-Arg) on brain morphology and function in mature albino rats exposed to antenatal hypoxia. Methods. Female rats were exposed to hypobaric hypoxia from gestation day 15 to day 19 day. The offspring was divided into 2 groups: 1) the first group, antenatal hypoxia (n = 12), where rats were injected with 0.1 ml of saline from 2 to 6 days of life, 2) the second group, antenatal hypoxia + dalargin (n = 17), where rats were injected with the peptide dalargin (100 mg/kg, i.p.) from 2 to 6 days of life. The control group (n = 25) included offspring of intact female rats. The size of neuronal nuclei and nucleoli in neocortical layers II and V and hippocampal area CA1 were measured on histological slides of the brain from 60-day old male rats. Intensity of free radical oxidation was determined by chemiluminescence in brain homogenates. Rat behavior was evaluated using the open field test and the elevated plus-maze test. Results. Antenatal hypoxia decreased body weight and weight of cerebral hemispheres in 60-day old male albino rats compared with the control. Antenatal hypoxia decreased the number of neuronal nucleoli in layer II of the neocortex and hippocampal area CA1, reduced neuronal nucleus size in layer V of the neocortex and the total area of neuronal nucleoli in all examined brain areas of 60-day-old male albino rats. Animals of this experimental group displayed increased motor activity. The chemiluminescence study of brain homogenates from 60-day-old animals showed increased free radical generation in brain tissues. Administration of dalargin reduced the morphofunctional cerebral consequences of antenatal hypoxia. Conclusion. Dalargin can be used for correcting long-term cerebral consequences of antenatal hypoxia.