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.
Rocha-de-Melo
Ana Paula
AP
Departamento de Nutrição, Universidade Federal de Pernambuco, BR-50670-901, Recife, PE, Brazil.
de Lima
Kalina Rimena
KR
de Albuquerque
Juliana da Mota Silveira
Jda M
de Oliveira
Andréa Kátia Prado
AK
Guedes
Rubem Carlos Araújo
RC
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling / Q000254:growth & development / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology*; D002908:Chronic Disease; D013181:Cortical Spreading Depression / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D008297:Male; D009270:Naloxone / Q000633:toxicity*; D009292:Narcotic Antagonists / Q000633:toxicity*; D018847:Opioid Peptides / Q000378:metabolism; D009293:Opioid-Related Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013995:Time
D009292:Narcotic Antagonists; D018847:Opioid Peptides; D009270:Naloxone