Long Term Effects of Fentanyl on Postnatal Breathing Patterns

McKay, L. C. and Kennedy, A. (2013) Long Term Effects of Fentanyl on Postnatal Breathing Patterns. Neuroscience 2013, San Diego, CA, USA, 9-13 Nov 2013.

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Abstract

The mammalian respiratory system is immature at birth. In mice, this immaturity is characterized by a fragile and highly variable breathing pattern during postnatal days 1-3 (P1-3). Around P4, the respiratory system undergoes a step in maturity, after which breathing is less variable and has a higher frequency. The neural mechanisms underlying this maturity step are unknown. The preBÖtzinger Complex (preBÖtC) and Retrotrapezoid nucleus/parafacial respiratory group play a critical role in generating respiratory rhythm but little is known of their interaction during development and early postnatal life when the respiratory system is fragile. Fentanyl, a µ-opioid receptor agonist was used to pharmacologically manipulate the opiate sensitive preBÖtC during early postnatal life and to investigate the long term effects on breathing of being exposed to opiates during this critical period of postnatal maturation. Neonatal mice were exposed to fentanyl (0.08mg/kg i.p daily), or saline as a control, from P1-5 (n=16) or P9-13 (n=16). Mice were continuously monitored post injection and breathing recorded by closed plethysmography at regular intervals from 5 minutes to 2 hours post injection. Fentanyl had a modest effect on breathing at all postnatal days by increasing variability, decreasing frequency (250±20 vs 150±30 breaths per minute) and increasing the number of apneas (2±1 vs 5±2 per minute), compared to saline-exposed mice. At 6 weeks of age, all saline and fentanyl exposed mice were exposed to a further dose of fentanyl (0.04 - 1.0mg/kg ip) and monitored as above. Respiratory frequency was significantly decreased (190±10 vs120±15 bpm, p<0.05) in all mice previously exposed to saline as neonates (P1-P5 and P9-13); however, in mice previously exposed to fentanyl as neonates (P1-P5 and P9-13), further fentanyl exposure in adulthood had no effect on respiratory frequency (180±8 vs 170±10 bpm). Tidal volume increased slightly in all mice post fentanyl regardless of whether they had previously been exposed to fentanyl or saline. These data suggest that the respiratory system in younger animals is less susceptible to fentanyl compared to adults and pre exposure to fentanyl during early postnatal maturation results in a long term desensitization to further fentanyl insults.

Item Type:Conference or Workshop Item
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McKay, Dr Leanne
Authors: McKay, L. C., and Kennedy, A.
Subjects:Q Science > QP Physiology
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
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