Given the social and ethical issues surrounding maternal neglect and abuse in humans, an animal model of neglect provides an important method to study the bio-behavioral underpinnings of maternal neglect/abuse with more direct control over the confounding variables found in human research. Child abuse and maternal neglect has long been strongly correlated with drug abuse in women. Recently, lower levels of oxytocin and cocaine use during pregnancy have also been associated with general feelings of anger and hostility and difficulty with infant attachment in women. In a rodent model, the investigators have found that chronic cocaine treatment during pregnancy and acute cocaine treatment in postpartum dams both increase maternal neglect, defined as the disruption of pup-directed maternal behavior. Chronic cocaine treatment also increases postpartum maternal aggression towards intruders to the extent that pups are often injured, while acute cocaine treatment decreases protection of pups from intruders. They have also observed that chronic cocaine treatment reduces levels of oxytocin in the medial preoptic area and amygdala at the same time periods that maternal behavior and maternal aggression, respectively, are maximally affected. The investigators hypothesize that chronic and acute cocaine treatment will result in differential and significant patterns of maternal neglect/abuse of offspring at different times across the lactation period. They will measure the frequency, duration and latency of maternal behavior and maternal aggression in rat dams during lactation and unprovoked aggressive behavior (postweaning) towards other rats following chronic cocaine, acute cocaine, and saline treatment (Study 1). They also hypothesize that prenatal exposure to chronic cocaine and acute cocaine will result in altered patterns of maternal/parental behavior and aggression in offspring. Male and female rat offspring prenatally exposed to no treatment, chronic cocaine, acute cocaine or saline treatment will be tested for maternal behavior, parental behavior (males), maternal aggression, and unprovoked aggression towards other rats as juveniles and adults (Study 2). To determine if rearing conditions (neglect versus nurturing) ameliorate or exacerbate the effects of prenatal exposure to cocaine, they will study the offspring of chronic cocaine, acute cocaine, saline treated or untreated dams who are reared with their natural mothers or cross-fostered to other untreated, or cocaine or saline treated mothers. Males and females will be tested for maternal/parental behavior, maternal aggression and unprovoked aggression as juveniles and adults (Study 3). Study 4 will determine if oxytocin system changes in relevant brain areas are correlated with behavioral differences between groups of dams and offspring by sacrificing rats after behavioral testing and measuring oxytocin levels in these regions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA013362-02
Application #
6379053
Study Section
Special Emphasis Panel (ZRG1-SSS-C (01))
Program Officer
Wetherington, Cora Lee
Project Start
2000-08-05
Project End
2004-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
2
Fiscal Year
2001
Total Cost
$268,008
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Psychiatry
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Williams, S K; Johns, J M (2014) Prenatal and gestational cocaine exposure: Effects on the oxytocin system and social behavior with implications for addiction. Pharmacol Biochem Behav 119:10-21
Johns, Josephine M; McMurray, Matthew S; Joyner, Paul W et al. (2010) Effects of chronic and intermittent cocaine treatment on dominance, aggression, and oxytocin levels in post-lactational rats. Psychopharmacology (Berl) 211:175-85
Williams, Sarah K; Cox, Elizabeth T; McMurray, Matthew S et al. (2009) Simultaneous prenatal ethanol and nicotine exposure affect ethanol consumption, ethanol preference and oxytocin receptor binding in adolescent and adult rats. Neurotoxicol Teratol 31:291-302
McMurray, M S; Cox, E T; Jarrett, T M et al. (2008) Impact of gestational cocaine treatment or prenatal cocaine exposure on early postpartum oxytocin mRNA levels and receptor binding in the rat. Neuropeptides 42:641-52
McMurray, M S; Joyner, P W; Middleton, C W et al. (2008) Intergenerational effects of cocaine on maternal aggressive behavior and brain oxytocin in rat dams. Stress 11:398-410
Johns, Josephine M; McMurray, Matthew S; Hofler, Vivian E et al. (2007) Cocaine disrupts pup-induced maternal behavior in juvenile and adult rats. Neurotoxicol Teratol 29:634-41
Johns, Josephine M; Elliott, Deborah L; Hofler, Vivian E et al. (2005) Cocaine treatment and prenatal environment interact to disrupt intergenerational maternal behavior in rats. Behav Neurosci 119:1605-18
Light, Kathleen C; Grewen, Karen M; Amico, Janet A et al. (2004) Deficits in plasma oxytocin responses and increased negative affect, stress, and blood pressure in mothers with cocaine exposure during pregnancy. Addict Behav 29:1541-64
Lubin, Deborah A; Elliott, Jay C; Black, Mitchell C et al. (2003) An oxytocin antagonist infused into the central nucleus of the amygdala increases maternal aggressive behavior. Behav Neurosci 117:195-201
Phillips, Paul E M; Johns, Josephine M; Lubin, Deborah A et al. (2003) Presynaptic dopaminergic function is largely unaltered in mesolimbic and mesostriatal terminals of adult rats that were prenatally exposed to cocaine. Brain Res 961:63-72

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