-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 important 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. We have completed treatment and harvesting of biological samples for the post-mortem studies. We have recruited all cohorts of monkeys, completed treatment and assessment of treatment in three of those. An additional cohort will complete the treatment phase of the study within the next 18 months. Core Resources: Core staff consulted closely on the preparation of a project proposal for funding by the office of Scientific Director, as well as being responsible for preparation of an Animal Studies Protocol for ACUC review. 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 sought 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 examined the role of gonadal steroids at puberty in the normal development of gene expression patterns in the primate prefrontal cortex. Behavioral and endocrine markers and structural MRI scans were examined before and for up to 2 years after gonadectomy or sham operations. Post puberty animals have been euthanized and brains harvested for post-mortem studies which are now ongoing. 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. -Depressogenic Effects of IFN-alpha, a cytokine cancer treatment agent. Summary: Recent evidence suggests IFN-alpha may induce symptoms of depression in humans and animal models. In the current studies we are collaborating with intramural and extramural scientists to examine the emergence of these symptoms in monkeys and to further characterize the neural processes associated using in vivo PET and MRI imaging technologies. Core Resources: Core staff was responsible for preparation of an Animal Studies Protocol for ACUC review. Core staff are (1) transport and testing of research subjects in a comprehensive behavioral battery;(2) responsible for training and assisting In Vivo Imaging project staff with preparation of subjects for imaging as well as (3) collection of biological fluids including blood and CSF as needed for endocrine markers;(4) responsible for training and assisting project staff with transport, temporary housing, anesthesia and life signs monitoring of research subjects during in vivo imaging sessions. Role of the intracellular protein p11 in the emergence of mood disorders. Summary: Recent evidence suggests levels of the intracellular protein p11 may be related to the emergence of depression in humans and animal models. In the current studies we are collaborating with intramural and extramural scientists to examine the emergence of these symptoms in monkeys and to further characterize the neural processes associated using viral vector, in vivo PET and MRI imaging technologies. Core Resources: Core staff was responsible for preparation of an Animal Studies Protocol for ACUC review. Core staff are (1) responsible for testing of research subjects in a behavioral battery and (2) responsible for transport, temporary housing, anesthesia and life signs monitoring of research subjects during in vivo imaging sessions and (3) assisting in the surgical preparation of subjects for central delivery of a AAV-p11 viral vector system for over production or inhibition of p11 in selected neural structures.. - Feasibility of transgenic models (lentiviral strategy) in marmoset monkeys. Summary: Genetic susceptibilities clearly contribute to the development of many psychiatric diseases. The primary objective of this project is to adapt newly developed lentiviral techniques to generate transgenic marmosets. Participants will 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. Core Resources: Core staff serves 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 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 use 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 has developed and validated ELISA based endocrine assay techniques for rapid determination of gonadal and HPA endocrine status for monkeys subjects in multiple projects. Core Resources: The Core has leased an ELIZA plate reader and has completed efforts to validate several hormone assay kits for non-human primates. - 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 extinction.
