The Effect of Maternal Cocaine Exposure on Neonatal Rat Cardiac Function

Abstract

Fetal cocaine exposure has been associated with a variety of cardiovascular dysfunctions in humans. We treated pregnant rats with either saline or cocaine at 60 mg/kg by gastric lavage for the entire gestational period and for 14 days after parturition. We then performed high-frequency transthoracic echocardiography to determine whether cocaine exposure affected neonatal cardiac contractile function in vivo in 7- and 14-day-old neonatal rats. All studies were performed in the unsedated, conscious state. Heart rate (HR) and systolic function, expressed as fractional area of change at the midpapillary muscle level, were calculated from two-dimensional images. Resting HR was faster in the cocaine-exposed group at both ages, but baseline contractile function was not different between control (CTL) and cocaine-exposed (COC) neonatal rats. Dobutamine induced a significant increase in HR in all groups at only the largest dose tested (Day 7 CTL HR increased from 438 +/- 3 bpm to 462 +/- 10 bpm; Day 7 COC HR increased from 466 +/- 3 bpm to 493 +/- 7 bpm; Day 14 CTL HR increased from 443 +/- 4 bpm to 487 +/- 4 bpm; Day 14 COC HR increased from 477 +/- 4 bpm to 501 +/- 5 bpm). Dobutamine elicited a significant increase in contractile response at both Day 7 (from 76.6% +/- 0.6% to 81.5% +/- 0.7%) and Day 14 in CTL (from 78.2% +/- 0.7% to 81.9% +/- 0.7%), but not in COC, animals (from 76.7% +/- 0.8% to 78.9% +/- 0.8% at Day 7 and from 76.8% +/- 1.1% to 79.3% +/- 0.8% at Day 14). Epinephrine induced a significant increase in contractile response in CTL, but not in COC, rats at Day 7 and had no effect on fractional area of change at 14 days of age in either CTL or COC animals. Our results indicate that perinatal cocaine exposure does not modify resting contractile function but attenuates the contractile response to beta-adrenoceptor stimulation in the neonatal rat. These results suggest that perinatal cocaine exposure may lead to decreased responsiveness to inotropic drugs during the early neonatal period.

Longitudinal Effects of Embryonic Exposure to Cocaine on Morphology, Cardiovascular Physiology, and Behavior in Zebrafish

“…The lower response to isoproterenol suggests that ß1-adrenergic signaling, which mediates much of the effects of cocaine on the heart in all species examined, was attenuated in response to early exposure ( Figure 4 A). Similar data have been reported for neonatal rats treated with cocaine in utero in which prenatal cocaine altered ß-adrenergic receptor expression, as well as downstream regulatory genes of the signaling pathway [ 47 , 48 ]. The cardiovascular response to cocaine of adult fish from the embryonic treatment groups was not significantly different than untreated controls ( p < 0.06).…”

Effect of prenatal cocaine on early postnatal thermoregulation and ultrasonic vocalization production

“…Body temperature regulation is a relatively unstudied effect of prenatal cocaine, but the presence of such effects is not necessarily surprising given the disturbances in cardiac development previously reported (Regalado et al, 1996; Sun et al, 2003) and prior reports of acute cocaine altering thermoregulation in adults (Crandall et al, 2002). On PND 3, the baseline T IS and T Back of cocaine-exposed pups was almost 2° (Celsius) warmer than untreated pups on average, and was maintained despite alterations in environmental temperatures.…”

The Housekeeping Gene (GA3PDH) and the Long Interspersed Nuclear Element (LINE) in the Blood and Organs of Rats Treated with Cocaine

“…The drug (carrier) was administered orally using a metal feeding needle. The dose of cocaine was chosen on the basis of extrapolation from published data from human subjects and validated in earlier animal experiments 10–12 . Newborn rats were left with their biological mothers for natural feeding and care.…”