Assessment of neural and behavioral alterations associated with chronic fluoxetine administration in adolescence. ? Summary: A major public health concern has emerged regarding the treatment of children with psychotherapeutic drugs. This study seeks to inform this imortant concern. A primate differential rearing model is used to assess the effects of chronic fluoxetine treatment of juvenile monkeys. Treatment and rearing history are hypothesized to interact in shaping developmental trajectories. The overall hypothesis for the study is that emotional behavior and neurobiology in adulthood are influenced both by exposure in childhood to differential rearing history and to psychotropic medications. An inter-institute User Committee reflecting 4 intramural and 2 extramural laboratories has been formed to manage integration of in vivo and post mortem research objectives. Studies include an initial study of fluoxetine pharmacokinetics, longitudinal studies of chronic fluoxetine effects in vivo, and studies of chronic fluoxetine effects on post-mortem measures of neural development (n=9). ? Core Resources: Core staff consulted closely on the preparation of a project proposal for review and funding by the office of Scientific Director, as well as being responsible for preparation of an Animal Studies Protocol for ACUC review. Staff subsequently negotiated for purchase of differentially reared research subjects from the NICHD breeding colony at the NIHAC to be acquired in three birth cohorts. Core staff are currently (1) responsible for daily scheduling, transport and testing of research subjects in a comprehensive behavioral battery; (2) responsible for periodic collection of biological fluids including blood and CSF as needed for drug level determinations and endocrine markers; (3) responsible for transport, temporary housing, anesthesia and life signs monitoring of research subjects during in vivo imaging sessions; (4) responsible for support of necropsy procedures associated with tissue harvest for post-mortem studies. ? ? Role of gonadal steroids at puberty in the development of orbital and medial prefrontal cortex of male rhesus macaques. ? Summary: Schizophrenia often emerges during or around puberty. This study seeks to characterize primate brain development during puberty as a potential risk factor for pathophysiology associated with schizophrenia. This collaborative project between 1 intramural and 1 extramural laboratory examines the role of gonadal steroids at puberty in the normal development of gene expression patterns in the primate prefrontal cortex (N= 12; Rhesus macaques). Behavioral and endocrine markers and structural MRI scans were examined before and continue to be examined for up to 2 years after gonadectomy or sham operations. Post puberty animals will then be euthanized and brains harvested for post-mortem studies. ? Core Resources: Core staff was responsible for preparation of an Animal Studies Protocol for ACUC review. Staff subsequently negotiated for purchase of research subjects from the NICHD breeding colony at the NIHAC to be acquired in two birth cohorts. Core staff are (1) responsible for training and assisting project staff in daily scheduling, transport and testing of research subjects in a comprehensive behavioral battery; (2) responsible for training and assisting project staff with periodic collection of biological fluids including blood and CSF as needed for endocrine markers; (3) responsible for training and assisting project staff with transport, temporary housing, anesthesia and life signs monitoring of research subjects during in vivo imaging sessions; (4) responsible for training and assisting project staff with support of necropsy procedures associated with tissue harvest for post-mortem studies. ? ? Feasibility of transgenic models (lentiviral strategy) in marmoset monkeys. Collaborative Project with NIMH, NINDS and NICHD. Summary: Genetic susceptibilities clearly contribute to the development of many psychiatric diseases. This project seeks to develop methods to examine strategic genetic mutations in a non-human primate. The primary objective of this project is to test the feasibility of newly developed lentiviral techniques to generate transgenic marmosets. Participants seek to adapt and use such techniques to produce transgenic marmosets that will carry and express in the germline a gene for a reporter molecule that can be easily be detected by genetic testing or by histological analysis. These animals will, in essence, prove the adapted concept works, thus allowing the establishment of a roadmap for producing specific transgenic models of human diseases that have no current parallel in non-human primate, translational research. ? Core Resources: Core staff serve primarily an advisory role for the initial phase of the project. In addition, the Core seeks to develop ELISA based endocrine assay techniques for rapid determination of of the reproductive phase of marmoset monkeys to support superovulation and transfection techiques developed in the transgenic core. In later phases of development Core Staff will develop assessment paradigms for phenotype characterization. ? Social cognition in differentially reared monkeys using eye-tracking. ? Summary: This pilot project seeks to develop non-invasive eye-tracking technology to examine alterations in face and object information processing associated with differential rearing experience or pharmacological treatment. This technology would potentially be incorporated into analyses designed to examine social and emotional deficits and treatment effects on existing primate models of psychopathology.? Core Resources: Core staff was responsible for preparation of an Animal Studies Protocol for ACUC review. Core staff is responsible for training and assisting project staff in daily scheduling, transport and testing of research subjects.? Hormone Assay services? ? Summary: The NHP Core seeks to develop and validate ELISA based endocrine assay techniques for rapid determination of gonadal and HPA endocrine status for monkeys subjects in multiple projects. Such services are available from several primate research centers however often not on a timely basis. Particularly for rapid determination of reproductive status for genetic transfection technologies, we anticipate the need for rapid intramural capacity.? Core Resources: The Core has leased an ELIZA plate reader and has undertaken efforts to validate several hormone assay kits for non-human primates in collaboration with assay service providers at the Yerkes and Wisconsin National Primate Research Centers.? ? Fear potentiation and fear inhibition in a monkey fear-potentiated startle paradigm. ? Summary: We continue a collaborative project with Dr. Mike Davis at Emory University to examine neural processes associated with the development of cued fear and the extinction and inhibition of cued fear. These processes are hypothesized to be critically important for the development and treatment of Post-traumatic Stress Disorder, and many mood and anxiety disorders.? Core Resources: Core staff prepared an Animal Studies Protocol for ACUC review. Core staff are (1) responsible for periodic scheduling, transport and testing of research subjects in fear potentiated startle paradigm. Twelve Rhesus macaques are recruited periodically from the NHP Core pilot study cohort for these studies
| Richards, A Brent; Morris, Richard W; Ward, Sarah et al. (2009) Gonadectomy negatively impacts social behavior of adolescent male primates. Horm Behav 56:140-8 |
| Nelson, Eric E; Winslow, James T (2009) Non-human primates: model animals for developmental psychopathology. Neuropsychopharmacology 34:90-105 |
| Antoniadis, Elena A; Winslow, James T; Davis, Michael et al. (2007) Role of the primate amygdala in fear-potentiated startle: effects of chronic lesions in the rhesus monkey. J Neurosci 27:7386-96 |
| Kikusui, Takefumi; Winslow, James T; Mori, Yuji (2006) Social buffering: relief from stress and anxiety. Philos Trans R Soc Lond B Biol Sci 361:2215-28 |
