1995 — 1999 |
Johns, Josephine M. |
R29Activity Code Description: Undocumented code - click on the grant title for more information. |
Oxytocin and Cocaine--Maternal Behavior and Aggression @ University of North Carolina Chapel Hill
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.
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1 |
2000 — 2003 |
Johns, Josephine M. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Cocaine and Maternal Neglect: Intergenerational Effects @ University of North Carolina Chapel Hill
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.
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1 |
2001 — 2005 |
Johns, Josephine M. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Cocaine &Maternal Aggression--Oxytocinergic Mechanisms @ University of North Carolina Chapel Hill
DESCRIPTION (applicant's abstract): Cocaine abuse by human mothers is correlated with a high incidence of child neglect and abuse. Gestational cocaine (COC) treatment has been shown to increase aggression towards an intruder (maternal aggression) and reduce the levels of oxytocin (OXY) in the amygdala of rats on postpartum days (PPD) 6-10. Blocking OXY receptors in the central amygdala results in an increase in aggression parallel to that seen following COC treatment. COC likely decreases OXY in the amygdala and increases maternal aggression through its reuptake inhibition of dopamine (DA), serotonin (5-HT) and norepinephrine (NE). These studies are designed to elucidate the specific mechanisms through which COC may work to alter OXY and maternal aggression in rats. Specific Aim 1 will determine if gestational treatment with a combination treatment of selective DA and 5-HT uptake inhibitor will increase maternal aggression as does COC. To test this hypothesis, groups of rat dams will be treated gestationally (days 1-20) with COC, control vehicle buffer (VCB), selective DA, 5-HT, or NE reuptake inhibitors or combinations of selective inhibitors. Dams will be tested for maternal aggression on PPD 6. Specific Aim 2 will determine if gestational treatment with a combination of a selective DA and 5-HT uptake inhibitor will alter OXY dynamics as does COC. To test this hypothesis, groups of rat dams will be treated gestationally (days 1-20) with vehicle buffer (VCB), COC, selective DA, 5-HT, or NE reuptake inhibitors or combinations of the selective inhibitors and sacrificed on PPD 6. OXY levels and receptor binding will be measured by radioimmunoassay, in situ hybridization and autoradiography in the amygdala, medial preoptic area and paraventricular nucleus of the hypothalamus, all of which have been implicated in OXY regulation of maternal aggression. Specific Aim 3 will determine if gestational COC treatment reduces OXY synthesis in the medial preoptic area and paraventricular nucleus and oxytocin receptor (OTR) synthesis in the amygdala, medial preoptic area and paraventricular nucleus. To test this hypothesis, rat dams will be treated gestationally with VCB or COC, and these brain regions removed for in situ hybridization and autoradiography for assessment of OXY and OTR messenger ribonucleic acid on PPD 6. Specific Aim 4 will determine if prenatal exposure to COC and being raised by a COC treated mother as compared to being raised by mothers treated with control vehicle increases maternal aggression displayed by female offspring and decreases OXY in the amygdala of the offspring as adults. To test this hypothesis, female offspring of dams gestationally treated with COC or control vehicle buffer (2 groups, buffer with no pair feeding and buffer with pair feeding), will be raised by their natural dams or foster dams that are vehicle-treated (pair-fed and non-pair-fed) or COC and then bred and tested for maternal aggression in the presence of their own litters on PPD 6. OXY levels in the amygdala will be assessed following the behavioral testing.
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1 |
2008 — 2012 |
Johns, Josephine M. |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Administrative Core @ University of North Carolina Chapel Hill
Address; Administrator; Advertising; Advisory Committees; Alcohols; Chemical Class, Alcohol; Clinical; Clinical Research; Clinical Study; Communication; Communities; Computers; Data; Data Security; Data awareness; Ensure; Evaluation; Feedback; Fellowship; Funding; Grant; Human Resources; Individual; Information Dissemination; Information Resources; Information Technology; Internet; Investigators; Knowledge; Leadership; Maintenance; Maintenances; Manpower; Medical; NIH; National Institutes of Health; National Institutes of Health (U.S.); Neurobiology; Neurodevelopmental Disorder; Neurological Development Disorder; Neurosciences Research; Numbers; Personnel Management; Phone; Programs (PT); Programs [Publication Type]; Protocol; Protocols documentation; Psychiatry; Psychology; R01 Mechanism; R01 Program; RPG; Recruitment Activity; Reporting; Research; Research Grants; Research Personnel; Research Project Grants; Research Projects; Research Projects, R-Series; Research Resources; Researchers; Resource Allocation; Resource Sharing; Resources; Rest; SCHED; Schedule; Security, Data; Series; Services; Students; Task Forces; Teleconferences; Telephone; Training; Transmission; United States National Institutes of Health; WWW; design; designing; information security; knowledge resource; member; neurobiological; outreach; personnel; programs; recruit; tool; transmission process; web; world wide web
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1 |
2008 — 2012 |
Johns, Josephine M. |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Cocaine: Effects On Neurobehavioral Determinants of Dam-Pup Interactions @ University of North Carolina Chapel Hill
0-11 years old; 8-Azabicyclo(3.2.1)octane-2-carboxylic acid, 3-(benzoyloxy)-8-methyl-, methyl ester, (1R-(exo,exo))-; Abuse, Cocaine; Acoustic Stimulation; Aged 65 and Over; Animal Model; Animal Models and Related Studies; Animals; Antidiuretic Hormone; Antidiuretic Hormones; Auditory; Behavior; Behavioral; Behavioral Mechanisms; Biological; Blood Plasma; Body Temperature; Brain; Brain region; Care giver Burden; Caregiver Burden; Caring; Cell Communication and Signaling; Cell Signaling; Characteristics; Chemicals; Chemotherapy-Hormones/Steroids; Child; Child Abuse and Neglect; Child Youth; Childhood maltreatment; Children (0-21); Chronic; Cocaine; Cocaine Abuse; Cognitive; Common Rat Strains; Complex; Computer information processing; Condition; Control Groups; Corticosterone; Cotton Plant; Crying; Cryings; Cues; Data; Development; Diffusion; Diffusion MRI; Diffusion Magnetic Resonance Imaging; Diffusion Weighted MRI; Dimensions; Discipline of Nursing; Disruption; Drug usage; Drugs; Elderly; Elderly, over 65; Encephalon; Encephalons; Endocrine; Endocrine Gland Secretion; Exhibits; Exposure to; FOS gene; Female; Fetal Cocaine Exposure; Fostering; G0S7; Gene Expression; Genes, Immediate-Early; Genetic; Genetic Polymorphism; Gestation; Gossypium; Heat Production; Hind Brain; History; Home; Home environment; Hormones; Hour; Human; Human, Child; Human, General; Hypothalamic structure; Hypothalamus; Image; Immediate-Early Genes; Incidence; Individual; Infant; Intracellular Communication and Signaling; Label; Magnetic Resonance; Mammals, Rats; Mammals, Rodents; Man (Taxonomy); Man, Modern; Maternal Behavior; Measures; Mechanisms of Behavior and Behavior Change; Mediator; Mediator of Activation; Mediator of activation protein; Medication; Memory; Mesencephalon; Mid-brain; Midbrain; Midbrain structure; Modeling; Mothers; Nerve Cells; Nerve Unit; Nervous System, Brain; Neural Cell; Neurobiology; Neurocyte; Neurohormones; Neurologic; Neurological; Neurons; Normal saline; Nursing; Nursing Field; Nursing Profession; OXT; Ocytocin; Oxytocin; Oxytocin Receptor; Pattern; Perception; Peripheral; Personal Satisfaction; Pharmaceutic Preparations; Pharmaceutical Preparations; Physiologic; Physiological; Plasma; Polymorphism (Genetics); Polymorphism, Genetic; Postpartum; Postpartum Period; Pregn-4-ene-3,20-dione, 11,21-dihydroxy-, (11beta)-; Pregnancy; Principal Investigator; Processing, Information; Production; Programs (PT); Programs [Publication Type]; Proteins; Protooncogene FOS; Range; Rat; Rate; Rattus; Recombinant Oxytocin; Recording of previous events; Regulation; Reporting; Research; Research Design; Response to stimulus physiology; Reticuloendothelial System, Serum, Plasma; Reunion; Reunion Island; Rhombencephalon; Rodent; Rodentia; Rodentias; Saline; Saline Solution; Secure; Serum, Plasma; Signal Transduction; Signal Transduction Systems; Signaling; Social Behavior; Social isolation; Sodium Chloride 0.9%; Stimulation, Auditory; Stimulus; Stress; Structure; Study Type; Temperature; Testing; Therapeutic Hormone; Thermogenesis; Thinking; Thinking, function; Time; Touch; Touch sensation; Ultrasonic; Ultrasonics; Urinary System, Urine; Urine; Vasopressins; Ventricular; Weight; Woman; advanced age; behavior test; behavioral test; beta-Hypophamine; biological adaptation to stress; biological signal transduction; c fos; c-fos Gene; c-fos Proto-Oncogenes; care giver stress; caregiver stress; child maltreatment; children; cocaine abuse in pregnancy; cocaine use in pregnancy; cotton; day; diffusion tensor imaging; drug use; drug/agent; elders; gene product; geriatric; gestational cocaine exposure; hindbrain; human study; hypothalamic; imaging; insight; late life; later life; male; model organism; myelination; neglect; neonate; neurobehavioral; neurobiological; neurobiological mechanism; neuronal; older adult; older person; olfactory stimulus; polymorphism; postnatal; preference; pregnant cocaine abuser; prenatal cocaine exposure; prenatal cocaine use; prenatal exposure; prenatally cocaine exposed; prenatally exposed; programs; pup; reaction; crisis; receptor expression; response; senior citizen; size; social; sociobehavior; sociobehavioral; stimulus/response; stress response; stress; reaction; study design; v-FOS FBJ Murine Osteosarcoma Viral Oncogene Homolog; vocalization; well-being; youngster
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1 |
2008 — 2015 |
Johns, Josephine M. |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Neurobiological and Behavioral Consequences of Cocaine Use in Mother/Infant Dyads @ Univ of North Carolina Chapel Hill
This program project is a multidisciplinary, translational research project employing animal and human projects to focus on the elucidation of neurobiological and behavioral characteristics and responses of mothers that have used primarily cocaine during pregnancy and of offspring prenatally exposed to cocaine that might impact negatively on normal mother-infant interactions. Although maternal cocaine use is known to be highly correlated with maternal neglect and poorer mother-infant interactions in both human and animal models, there is little direct research on perceptual, endocrine and neurological responses of these women when presented with relevant infant cues (cries, touch, pictures). Similarly, little is known about abnormal physiological/behavioral responses in infants prenatally exposed to cocaine that may impact parenting behaviors of both drug using and non-using mothers. One animal, and 2 human clinical projects will address three main hypotheses which address the possibility that cocaine use by mothers and/or prenatal exposure to cocaine in offspring could result in drug-induced neurological and/or bio-behavioral abnormalities in both, that contribute to neglect and poor mother-infant interactions in animals and humans. The animal project will assess specific characteristics of infant stimuli or behavior (vocalizations, thermoregulatory ability, olfactory cues, response to mothers presence) and brain structural abnormalities (regional, ventricular differences) and gene expression as well as measuring differential maternal behavioral and endocrine responses to and preference for exposed compared to non-exposed infants or stimuli produced by infants. The human projects will focus on perceptual, endocrine and behavioral responses to stress related and infant related stimuli and infant response to mothers, as well as infant brain structural and pathway developmental abnormalities (project 2) and (project 3) measurement of maternal (fMRI) endocrine and neurological brain regional responses to infant stimuli (cries, visual vignettes). We hypothesize differences in behavioral, physiological and/or neurological characteristics (infant cries, infant stimulus cues, physical elicitation of care and brain structural abnormalities) of both human and rodent offspring (prenatally drug exposed versus non-exposed), which could result in differential maternal response. We predict that mothers who have abused cocaine will exhibit differences in perceptual, behavioral, endocrine and/or neurological responses to relevant infant stimuli compared to non-drug users. This translational, interdisciplinary project will allow researchers from different research backgrounds and expertise to work together to better identify specific attributes of mothers and infants that could contribute to a better understanding of how drugs of abuse specifically and particular characteristics of individuals in general may influence neglect. This could result in early and continuing intervention strategies to offset some of the negative consequences in this population.
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1 |
2010 — 2011 |
Johns, Josephine M. |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Mr Microscopy of a Rat Prenatal Cocaine Exposure Model
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We are explorng the developmental effects of prenatal cocaine exposure in a rat model. Little data actually exist regarding the effects of cocaine during development, thus the need for such studies are great. Here at UNC, we are doing high-resolution DTI scans, but the facilities here are not equipped to do ultra-high resolution MR microscopy. Thus, we have discussed with Al Johnson the potential to explore this aim at Duke. Our DTI studies are currently performed in rat mothers treated with cocaine on postpartum day 5, and in the male and female offspring of these mothers on postnatal days 5 and 14, roughly trnaslational to the end of the third trimester and approximately 1 week old in human development. If differences in brain structure are found at these time points, we are interested in exploring later time points to determine the long term developmental effects of prenatal cocaine exposure.
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0.97 |