Effects of Subchronic versus Acute in utero Exposure to Dexmedetomidine on Foetal Developments in Rats

Abstract: Dexmedetomidine is a highly selective and specific α-2 adrenergic agonist with sedative, analgesic and sympathetic activities. This study was undertaken to investigate the effects of in utero exposure of dexmedetomidine on foetal development and postnatal behaviour in the offspring. Pregnant Sprague-Dawley rats were chronically treated with dexmedetomidine (0, 5, 10 and 20 µg/kg, subcutaneously) daily from gestation day 7 to day 19. Another group of animals received only a single acute dose of dexmedetomidine (20 µg/kg) on gestational day 19 to mimic a model for systemic analgesia during labour. Administration of dexmedetomidine did not affect the frequency of implantations. Chronic administration of 10 and 20 µg/kg of dexmedetomidine significantly reduced the body weight and crown-rump length of pups, whereas a single acute dose (20 µg/kg) did not affect these parameters. None of the pups exhibited any external malformations or skeletal abnormalities irrespective of treatment assigned. All the pups showed a normal postnatal weight gain during the developmental phase. No significant differences were observed among any of the groups with respect to behavioural performances of offspring in beam balance, grip strength and inclined plane tests as well as motor activity. In conclusion, acute exposure to dexmedetomidine at the anticipated delivery time does not exert any adverse effects on perinatal morphology of pups, their birth weight, crown-rump length, physical growth and postnatal behavioural performances. Since this study was conducted in rats, its clinical relevance in human beings remains to be unclear and warrants further studies.