Chronic maternal morphine alters calbindin D-28k expression pattern in neonatal mouse brain

Introduction: Calcium-binding proteins such as calbindin (CB), parvalbumin (PV) and calretinin, widely present in the mammalian brain, are presumed to buffer elevated intracellular calcium levels associated with ischemia, epilepsy or excitation and acting as endogenous protective proteins. Our earlier study on chronic morphine effects on PV expression in developing mouse brain indicated alterations in the patterns of PV immunoreactivity (IR) in specific brain regions. Herein we have studied the influence of chronic maternal morphine on Calbindin D- 28k expression in brain regions earlier observed to reveal alterations in PV-IR. Methods: Female Swiss Mice were daily administered saline or morphine (30 or expression60 mg/kg body weight) for a period comprising 7 days before mating, during gestation and until 21 day post-partum. Their pups were sacrificed on postnatal day 18 and coronal sections of their brains were examined by histological staining of cresyl violet and for CB-immunoreactivity. Results: Histology revealed no significant changes in the cell number of the morphine-treated neonatal forebrain. However the number of CB-positive neurons decreased remarkably in the anterior cingulate cortex, in layers IIIV of the parietal cortex I and in CA1 and CA2 regions of the hippocampus; and increased in layers V-VI of the parietal cortex I and in the subicular region. Conclusions: These effects of morphine on calbindin-immunoreactivityin areas like the cingulate and parietal I cortices and the hippocampus of neonatal mouse confirm the key roles played by these structures in the behavioural patterns of the maternally addicted neonates, such as impaired somatosensory, cognitive, learning and memory performances. The molecular mechanisms of morphine action on CB in neonatal mouse brain are not evident, but alterations in the expression patterns of calcium binding proteins in specific regions of the developing brain might be one of the mechanisms by which addictive drugs modify the functionality of developing brain. Approved by the Veterinary Scientific Committee of the University of Naples Federico II (art. 3 D.LVO 116/ 92) ©