title: Breathing and temperature control disrupted by morphine and stabilized by clonidine in neonatal rats.
abstract: BACKGROUND
  Sedative-analgesics are often given to newborn infants and are known to affect many components of the autonomic nervous system. While morphine is most frequently used, α-2 adrenergic receptor agonists are being increasingly used in this population. Alpha-2 adrenergic receptors agonists also have anti-shivering properties which may make it a desirable drug to give to infants undergoing therapeutic hypothermia. The aim of this study was to systematically compare two different classes of sedative-analgesics, morphine, a μ-opioid receptor agonist, and clonidine an α-2 adrenergic receptor agonist on breathing, metabolism and core body temperature (CBT) in neonatal rodents.
  
  
  METHODS
  Breathing parameters, oxygen consumption (VO2) and carbon dioxide production (VCO2), were measured prior to, 10 and 90 min after intraperitoneal (IP) administration of morphine (2, 10 or 20 mg/kg), clonidine (40, 200 or 400 μg/kg), or saline in Sprague-Dawley rat pups at postnatal day 7 (p7) while continuously monitoring CBT.
  
  
  RESULTS
  Morphine reduced the respiratory rate, VO2 and VCO2 greater than clonidine at all dosages used (p<0.05, morphine vs. clonidine, for all metabolic and respiratory parameters). Furthermore, morphine induced prolonged respiratory pauses, which were not observed in animals treated with clonidine or saline. Morphine caused hypothermia which was dose dependent, while clonidine stabilized CBT in comparison to saline treated animals (p<0.0001).
  
  
  CONCLUSIONS
  In the newborn rat, morphine causes profound respiratory depression and hypothermia while clonidine causes minimal respiratory depression and stabilizes CBT. All together, we suggest that clonidine promotes autonomic stability and may be a desirable agent to use in infants being treated with therapeutic hypothermia.
authors.affiliation: Pediatrics, Johns Hopkins Medical Institutions, Baltimore, MD, United States.
authors.forename: Kalpashri
authors.initials: K
authors.lastname: Kesavan
authors.affiliation: Pediatrics, Johns Hopkins Medical Institutions, Baltimore, MD, United States.
authors.forename: Tarrah
authors.initials: T
authors.lastname: Ezell
authors.affiliation: Environmental Health Sciences, School of Public Health of Johns Hopkins, Baltimore, MD, United States.
authors.forename: Alexis
authors.initials: A
authors.lastname: Bierman
authors.affiliation: Universidade Nova de Lisboa, Portugal.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Nunes
authors.affiliation: Pediatrics, Johns Hopkins Medical Institutions, Baltimore, MD, United States.
authors.forename: Frances J
authors.initials: FJ
authors.lastname: Northington
authors.affiliation: Environmental Health Sciences, School of Public Health of Johns Hopkins, Baltimore, MD, United States.
authors.forename: Clarke G
authors.initials: CG
authors.lastname: Tankersley
authors.affiliation: Pediatrics, Johns Hopkins Medical Institutions, Baltimore, MD, United States. Electronic address: egauda@jhmi.edu.
authors.forename: Estelle B
authors.initials: EB
authors.lastname: Gauda
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D001831:Body Temperature / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007035:Hypothermia / Q000139:chemically induced* / Q000188:drug therapy; D009020:Morphine / Q000494:pharmacology / Q000633:toxicity*; D009294:Narcotics / Q000494:pharmacology / Q000633:toxicity*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D009294:Narcotics; D002245:Carbon Dioxide; D009020:Morphine; D003000:Clonidine
keywords: Clonidine; Hypothermia; Metabolism; Morphine; Respiratory depression; Sedative-analgesics