Ventilatory control in newborn mice prenatally exposed to cocaine.
Infants born to mothers who used cocaine during pregnancy are at increased risk for neonatal death and respiratory impairments. Confounding factors such as multiple substance abuse make it difficult to isolate the effects of cocaine. We used a murine model to test the hypothesis that prenatal cocaine exposure may impair ventilatory responses to chemical stimuli in newborns. Seventy-two pregnant mice were randomly assigned to three groups: cocaine (COC), saline (SAL), and untreated (UNT). COC and SAL mice received subcutaneous injections of either 20 mg/kg of cocaine or a saline solution twice a day from gestational days 8-17. Ventilation (V'(E)) and tidal volume (V(T)), both divided by body weight, and breath duration (T(TOT)) were measured using whole-body plethysmography in freely moving COC (n = 47), SAL (n = 123), and UNT (n = 93) pups on postnatal day 2.The comparison between SAL and UNT pups showed significant differences in baseline breathing and in V'(E) responses to hypoxia, suggesting that maternal stress caused by injections affected the development of ventilatory control in pups. Baseline T(TOT) was significantly longer in COC than in SAL pups. V'(E) responses to hypoxia were significantly smaller in COC than in SAL pups (+27 +/- 35% vs. +38 +/- 25%), but V'(E) responses to hypercapnia were similar (29 +/- 15% vs. 25 +/- 23%).Thus, breathing control was impaired by prenatal cocaine exposure, possibly because of abnormal development of neurotransmitter systems, such as the dopamine and serotonin systems.
Autret
Fanny
F
Laboratoire de Neurologie et Physiologie du Développement, INSERM E9935, Hôpital Robert Debré, Paris, France.
Dauger
Stéphane
S
Renolleau
Sylvain
S
Eng
Guy Vardon
GV
Kosofsky
Barry E
BE
Gressens
Pierre
P
Gaultier
Claude
C
Gallego
Jorge
J
D000818:Animals; D000831:Animals, Newborn; D001143:Arousal / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D005260:Female; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D051379:Mice; D010993:Plethysmography, Whole Body; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012123:Pulmonary Ventilation / Q000187:drug effects
D003042:Cocaine