Buprenorphine blocks withdrawal in morphine-dependent rat pups.
BACKGROUND
Infants placed on extracorporeal membrane oxygenation (ECMO) or mechanical ventilation often need continuous morphine infusions for pain relief and sedation. The resulting physical dependence requires an additional 2-3-week hospital stay to taper the morphine to avoid withdrawal. Buprenorphine effectively blocks abstinence in dependent adults, and in infants it could accelerate or eliminate the tapering schedule, thereby enabling earlier hospital dismissals.


METHODS
Morphine-dependent infant rats were used in this study to determine the effectiveness of buprenorphine in blocking abstinence. Postnatal day-14 (P14) rats were implanted with osmotic minipumps that delivered saline (1 microl x h(-1)) or morphine (2 mg x kg(-1) h(-1)) for 72 h. The minipumps were then removed to allow the rats to undergo spontaneous morphine withdrawal.


RESULTS
The withdrawal period lasted approximately 72 h out of a 96-h observation period. The following signs were significant during these hours: wet-dog shakes, 1-72 h; abdominal stretches, 1-72 h; forepaw tremors, 1-24 h; splayed hind-limbs, 1-72 h; ptosis, 4-72 h; and evoked vocalization, 4 and 8 h. A single 1 mg x kg(-1) buprenorphine dose significantly decreased wet-dog shakes from 1 to 72 h, abdominal stretches from 1 to 48 h, forepaw tremors and splayed hind-limbs 1-8 h, and ptosis and evoked vocalization at 4 and 8 h. Repeated administration of 1 mg x kg(-1) buprenorphine before pump removal and at 24, 48 and 72 h resulted in a greater magnitude of blockade of abstinence throughout the 96-h observation period.


CONCLUSIONS
Buprenorphine may prove to be a suitable drug for treating opioid withdrawal in human infants.
Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Dawn C
DC
Stoller
Forrest L
FL
Smith
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D009021:Morphine Dependence / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D002047:Buprenorphine; D012965:Sodium Chloride; D009020:Morphine