Project 1 (Animal) - Cocaine: Effects on Neurobehavioral Determinants of Dam-Pup Interactions

Principal Investigator: Josephine Johns, PhD

Project 1 (Animal) - Schematic


Cocaine abuse in women is correlated with a high incidence of child neglect and abuse.  Young children prenatally exposed to cocaine are reported to exhibit early signs of neurobehavioral stress, including excessive and high-pitched crying, increased state lability, decreased responsiveness to caregivers, stress-related behavioral differences, and poor social behavior in later life.  Animal models can more directly assess the neurobiological and behavioral mechanisms of drug-treated dams and their drug exposed offspring than can human studies, and can be informative for the focus of human research.

Research on the effects of cocaine exposure on early brain development and behavior of offspring that may alter maternal behavior (MB) is relatively sparse.  Using a rat model of cocaine-induced maternal neglect, we recently reported that chronic gestational cocaine (CC) treatment decreased.

MB towards their own and non-treated pups, but that CC-treated and control mothers exhibited less MB towards cocaine-exposed pups in the early postpartum period.  It is well documented that rodent mothers attend to specific stimuli of pups such as vocalizations, body temperature, nursing elicitation through touch, and olfactory stimulus cues.  Thus, these findings suggest that specific characteristics of CC-exposed pups may elicit differential care from dams.

It has also been shown that baby cries are perceived as less urgent by human mothers using cocaine than non-cocaine using mothers, suggesting that cocaine use may alter a mother’s ability to attend to specific stimuli from their babies.  Together, these data indicate that cocaine-induced changes in both mothers and offspring can influence maternal/infant interactions, although little is known about the behavioral or biological mechanisms underlying these effects.

Several possible biological mediators of cocaine’s effects on aspects of mother-infant interaction include stress related hormones such as oxytocin, vasopressin and corticosterone.  Oxytocin (OT), a neurohormone particularly important for normal maternal, affiliative, and stress response behaviors in animals, has been found to be reduced in brain regions important for normal MB, in CC-treated rat dams who display MB disruptions and in offspring who are less social.

Interestingly, data indicated that women with a history of cocaine abuse have lower plasma levels of OT, are less likely to pick up their babies at home, and have a different endocrine stress response pattern than do mothers with no drug history.  The proposed studies are designed to determine:

  1. if cocaine-exposed (CC) pups exhibit aberrations in pup-produced stimuli that could influence elicitation of MB in the early postnatal period;

  2. how the effects of CC or control treatments (untreated-UN, saline treated-CS) influences a dam’s responses to stimuli or behavior produced by CC-treated or control pups; and

  3. if there are physiological, endocrine, neurological, or genetic expression differences correlated with stimuli produced by pups or behavioral responses by dams that could suggest mechanisms responsible for disruption of mother-infant interactions in the early postpartum period when maternal care is so vital.

 

Key Personnel:

NAME ORGANIZATION ROLE ON PROJECT
Johns, Josephine, PhD UNC-Chapel Hill Principal Investigator
Blumberg, Mark, PhD University of Iowa Consultant
Boccia, Maria, PhD UNC-Chapel Hill Collaborator
Duncan, Gary, PhD UNC-Chapel Hill Collaborator
Farrell, William, PhD Queens College [NY] Consultant
Lin, Weili, PhD UNC-Chapel Hill Co-Investigator
Malanga, C J, MD, PhD UNC-Chapel Hill Co-Investigator
Morrell, Joan, PhD Rutgers University [NJ] Consultant
Moy, Sheryl, PhD UNC-Chapel Hill Co-Investigator
Styner, Martin, PhD UNC-Chapel Hill Co-Investigator
Zeskind, Philip (Sandy), PhD UNC-Chapel Hill Collaborator

 

Imaging Consultants:

NAME ORGANIZATION
Mori, Susumu, PhD Johns-Hopkins University [MD]
Sled, John, PhD McKinsey International College - Toronto [ONT]
Tyszka, Mike, PhD Cal Tech University [CA]

 

Graduate Students:

NAME ORGANIZATION
Cox, Beth UNC Neurobiology Curriculum
Jarrett, Thomas UNC School of Medicine MD/PhD Program
McMurray, Matthew UNC Department of Psychology
Williams, Sarah UNC Neurobiology Curriculum

 

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