Cocaine abuse in human mothers is correlated with a high incidence of child abuse and maternal neglect. We have found that cocaine (COC) treatment decreased maternal behaviors (MB) and increased postpartum maternal aggression (MAG) towards an intruder. In rats, oxytocin (OXY) has been shown to induce the onset of MB and is thought to influence MAG. We have also observed that COC treatment in rat dams reduced levels of OXY in several brain sites thought to be important in MB (hippocampus) and MAG (amygdala). It has been found that OXY working perhaps through the dopaminergic system attenuates several COC induced behaviors. We hypothesize that COC will cause a significant change in the frequency, duration, latency or patterning of specifically designated MB and nonsignificant changes in non-MB rather than significant differences in only non-MB. We will measure frequency, duration, latency and sequence of maternal and nonmaternal behaviors in COC treated postpartum rat dams (Study 1). We also hypothesize that alterations seen in MB and MAG are not simply a result of withdrawal from COC. To test this hypothesis MB and MAG will be measured in postpartum rat dams under conditions of COC withdrawal and non-withdrawal (Study 2). To determine if the increase in COC-induced aggression towards an intruder is directly related to the postpartum endocrine state or contact with pups, we will study aggression in COC treated rats which are virgins, lactating dams with pups present and lactating dams without pups (Study 3). We hypothesize that COC induced increases in aggression are not dependent upon lactational state or pup contact. Studies 4 and 5 will help to determine if, as hypothesized, OXY and COC are interacting, through the dopaminergic system, to alter MB and MAG. To test this hypothesis we will: (1) attempt to block the effects of COC on MB and MAG with OXY (2) attempt to produce alterations in MB and MAG similar to those produced by COC treatment by administering an OXY antagonist (OTA) and a dopamine reuptake inhibitor (amfonelic acid).(3) measure changes in OXY binding, levels and release in COC treated rat dams and (4) measure dopamine uptake in rat dams administered OXY.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29DA008456-01A2
Application #
2120946
Study Section
Special Emphasis Panel (SRCD)
Project Start
1995-03-15
Project End
2000-02-29
Budget Start
1995-03-15
Budget End
1996-02-29
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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; Williams, S K; Jarrett, T M et al. (2008) Gestational ethanol and nicotine exposure: effects on maternal behavior, oxytocin, and offspring ethanol intake in the rat. Neurotoxicol Teratol 30:475-86
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
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
Lubin, D A; Meter, K E; Walker, C H et al. (2001) Dose-related effects of chronic gestational cocaine treatment on maternal aggression in rats on postpartum days 2, 3, and 5. Prog Neuropsychopharmacol Biol Psychiatry 25:1403-20
Lubin, D A; Meter, K E; Walker, C H et al. (2001) Effects of chronic cocaine administration on aggressive behavior in virgin rats. Prog Neuropsychopharmacol Biol Psychiatry 25:1421-33
Light, K C; Smith, T E; Johns, J M et al. (2000) Oxytocin responsivity in mothers of infants: a preliminary study of relationships with blood pressure during laboratory stress and normal ambulatory activity. Health Psychol 19:560-7
Overstreet, D H; Moy, S S; Lubin, D A et al. (2000) Enduring effects of prenatal cocaine administration on emotional behavior in rats. Physiol Behav 70:149-56
Nelson, C J; Meter, K E; Walker, C H et al. (1998) A dose-response study of chronic cocaine on maternal behavior in rats. Neurotoxicol Teratol 20:657-60

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