Respiratory effects of chronic in utero methadone or morphine exposure in the neonatal guinea pig.
This study uses a neonatal guinea pig model to compare the effects of in utero methadone or morphine exposure upon breathing control. We hypothesize that in utero methadone exposure will result in similar respiratory disturbances to those seen in morphine exposed neonates, but that the onset will be slower and the duration longer, due to methadone's longer elimination half-life. Pregnant Dunkin-Hartley guinea pigs received once-daily injections of methadone, morphine, or vehicle (saline) during the last half of gestation and pups were studied 3, 7, or 14 days after birth. In utero methadone or morphine exposure resulted in decreased birth weight compared to vehicle, and pups experienced a withdrawal syndrome which included increased locomotor activity and respiratory disturbances but no change in rectal temperature. Both opioid exposures increased inspiratory minute ventilation during CO(2) challenge at 3 days after birth, but only in morphine exposed pups was this withdrawal effect still present on day 7. Surprisingly, only morphine exposure increased inspiratory minute ventilation during room air breathing. We conclude that in utero methadone exposure is not equivalent to in utero morphine exposure. With respect to neonatal respiratory control, methadone-induced changes in respiration are only apparent during hypercapnia.
Nettleton
Rosemary T
RT
Department of Physiology and Pharmacology, School of Medicine, Oregon Health & Science University, Portland, OR, USA.
Wallisch
Michael
M
Olsen
George D
GD
D000818:Animals; D000831:Animals, Newborn; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D006168:Guinea Pigs; D006207:Half-Life; D006935:Hypercapnia / Q000150:complications / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008691:Methadone / Q000633:toxicity*; D009020:Morphine / Q000633:toxicity*; D009294:Narcotics / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology; D012125:Respiratory Center / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology*; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000503:physiopathology; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D036401:Toxicity Tests, Chronic
D009294:Narcotics; D009020:Morphine; D008691:Methadone