Early malnutrition attenuates the impairing action of naloxone on spreading depression in young rats.

OBJECTIVES: Malnutrition early in life can disrupt neurotransmitter systems in the brain, affecting its electrophysiological function. The opioid receptor antagonist naloxone can affect the electroencephalogram (EEG) and behavior in animals and humans, and patients under drug-abuse treatment use it as a therapy. The goal of this work in the rat is to determine whether malnutrition early in life modulates the action of naloxone on the excitability-related phenomenon known as cortical spreading depression (CSD). METHODS: Malnutrition was induced by feeding the dams during the gestation and lactation with a low-protein diet (8% protein). Their male pups received a single daily subcutaneous injection of naloxone (10 mg/kg/day) from the 7th to the 28th postnatal day, and were subsequently (30-40 days of life) submitted to a 4-hours CSD recording session, with electrodes at two points at a fixed distance apart on the parietal cortical surface. RESULTS: Compared to well-nourished rats receiving a 23% protein diet, malnourished animals displayed lower body weights and higher CSD velocities of propagation, confirming the facilitating effect of malnutrition on CSD. Naloxone treatment reduced in well-nourished rats the CSD propagation velocity, as compared to saline-injected controls. In contrast, the naloxone effect was less intense in the malnourished condition, and the CSD velocity difference between malnourished-naloxone and malnourished-saline groups did not reach statistical significance. DISCUSSION: Data strongly support the involvement of opioid-based mechanisms in excitability-related neural processes, which probably influence CSD propagation, and indicate that early malnutrition attenuates the impairing action of naloxone on CSD.

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

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.