Chronic neonatal exposure of rats to the opioid antagonist naloxone impairs propagation of cortical spreading depression in adulthood

Abstract

Naloxone is an opioid receptor antagonist with effects on the EEG and behavior in animals and humans and has been used clinically in drug-abuse treatment. The goal of this work in the rat is to determine whether treatment with naloxone during the suckling period would influence the propagation of cortical spreading depression (CSD), both in weaned young and adult animals. From the 7th to the 28th postnatal day, male rat pups were treated daily with a single subcutaneous injection of either 10mg/kg/d naloxone (n=21 rats) or equivalent volume (10ml/kg) of saline (n=16). In both treatment conditions, when the pups were 30-40 days- (young groups; 9 Naloxone- and 10 saline-treated rats), or 90-120-days old (adult groups; 12 Naloxone- and 6 saline-treated rats), a 4h CSD recording session was performed with electrodes at two points at a fixed distance apart on the parietal cortical surface. CSD propagation velocity was calculated based on the time spent for a CSD-wave to pass between the electrodes. In both young- and adult groups, naloxone-treated animals displayed lower CSD velocities (P<0.05) than the corresponding saline injected animals. Our results demonstrate, for the first time, that chronic neonatal exposure of rats to the opioid antagonist naloxone results in an impairing propagation of the CSD that is long lasting, suggesting the existence of one or more opioid-mediated processes influencing CSD.