Translational Analysis of Effects of Prenatal Cocaine Exposure on Human Infant Cries and Rat Pup Ultrasonic Vocalizations

Abstract

Spectral and temporal features of human infant crying may detect neurobehavioral effects of prenatal cocaine exposure (PCE). Finding comparable measures of rodent ultrasonic vocalizations (USVs) would promote translational analyses by controlling the effects of correlated variables that confound human studies. To this end, two studies examined the sensitivity of similar acoustic structures in human infant and rat pup vocalizations to effects of PCE. In Study 1, cry sounds of 107 one month-old infants were spectrum analyzed to create a novel set of measures and to detect the presence of hyperphonation - a qualitative shift to an atypically high fundamental frequency (basic pitch) associated with neurobehavioral insult. Infants with PCE were compared to infants with prenatal polydrug-exposure (PPE) without cocaine and with infants in a standard comparison (SC) group with no prenatal drug exposure. In Study 2, USVs of 118 five day-old rat pups with either PCE, prenatal saline exposure or no prenatal exposures were spectrum analyzed to detect the presence of frequency shifts – acoustic features that have a frequency waveform similar to that of hyperphonation. Results of study 1 showed PCE had two sets of sex-dependent effects on human infants: PCE males had higher pitched cries with more dysphonation (turbulence); PCE females had longer pauses between fewer cry sounds that were of lower amplitude than comparison groups. PCE and PPE infants had more cries with hyperphonation than SC infants. In study 2, PCE pups had a greater percentage of USVs with shift in the acoustic structure than pups in the two control groups. As such, the novel measures of human infant crying and rat pup USVs were sensitive to effects of PCE. These studies provide the first known translational analysis of similar acoustic structures of vocalizations in two species to detect adverse effects of prenatal drug exposure.

Use of fast-scan cyclic voltammetry to assess phasic dopamine release in rat models of early postpartum maternal behavior and neglect

“…For example, pup urine is a strong stimulus that elicits MB (Londei et al, 1989), and in this study we demonstrate significant differences in the urine composition between cocaine-naïve and exposed pups. Also, ultrasonic vocalizations are altered by prenatal cocaine in rats (Cox et al, 2012, Lippard et al, 2015, McMurray et al, 2013) in ways that are qualitatively similar to exposed human infants (Zeskind et al, 2014). Therefore, it is feasible that stimuli produced by cocaine-exposed pups are less effective to evoke dopamine release in rat mothers.…”

“…The 2013 National Survey on Drug Use and Health found that 5.4% of pregnant women in the US were using illicit drugs, including cocaine (SAMHSA 2014). Affecting both mother and fetus, prenatal cocaine use has linked to deficits in infant development and maternal care in humans (Burns et al, 1991; Kelley et al, 1991; Murphy et al, 1991; Williams-Petersen et al, 1994; Mayes et al, 1997; Strathearn and Mayes 2010; Rutherford et al, 2011; Cain et al, 2013; Liu et al, 2013; Chiriboga et al, 2014; Grewen et al, 2014) and in rats (Johns et al, 2005; McMurray et al, 2013; Zeskind et al, 2014; McMurray et al, 2015; Lippard et al, 2015). As cocaine targets monoamine transporters, including the dopamine transporter, phasic dopamine transmission in cocaine-exposed mothers may be compromised.…”

Perinatal high‐fat diet impairs pup retrieval and induces sex‐specific changes in ultrasonic vocalization characteristics of rat pups

“…Abrupt discontinuous frequency changes, termed frequency shifts, are a feature of the cries of human infants and USVs in rat pups that were prenatally exposed to cocaine (Zeskind et al, ). These calls were also proposed to alter maternal attention and arousal, which elicit differential caregiving responses (Zeskind et al, ). For example, in humans, cocaine‐using mothers respond with withdrawal to these cries compared to non‐using mothers (Zeskind et al, ).…”

“…These calls were also proposed to alter maternal attention and arousal, which elicit differential caregiving responses (Zeskind et al, ). For example, in humans, cocaine‐using mothers respond with withdrawal to these cries compared to non‐using mothers (Zeskind et al, ). Although maternal malnutrition in the form of protein restriction during gestation does not appear to affect the number of USVs, it reduces the range of call types emitted by the pups during early postnatal life (Tonkiss et al, ).…”

Automatic segmentation of infant cry signals using hidden Markov models

“…Atypicalities in specific features of cry (e.g., fundamental frequency) have been linked with diagnosed conditions such as autism, developmental delays, and chromosome abnormalities [5,6] and with risk factors such as prematurity and prenatal drug exposure [7,8]. These findings have generated hope that cry analysis may offer a cost-effective [9], low-risk, and non-invasive [10,11] diagnostic technique for early identification of children with developmental and health problems.…”