-Assessment of neural and behavioral alterations associated with chronic fluoxetine administration in adolescence. Summary: 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. Core Resources: Core staff was responsible for preparation of an Animal Studies Protocol for ACUC review. Core staff are(1)responsible for daily scheduling, transport and testing of research subjects in a behavioral battery(2)responsible for collection of biological fluids including blood and CSF as needed for drug level determinations and endocrine markers(3)responsible for temporary housing, anesthesia and life signs monitoring of research subjects during in vivo imaging sessions(4)responsible for support of 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: 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 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 still being processed. Core Resources: Core staff was responsible for preparation of an Animal Studies Protocol for ACUC review. 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. We collaborated 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. This study has been completed. 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. The pilot study has been completed, post-mortem analysis is ongoing. 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, behavioral and endocrine monitoring, 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. -Behavioral phenotyping in marmoset monkeys. Summary: To support transgenic projects in marmosets currently being developed in the IRP Transgenic Core. Core staff will work with internal collaborators to develop a battery of behavioral, endocrine and cognitive tests for assessing differences between normal and transgenic animals. This project is ongoing. Core Resources: Core staff is responsible for building or obtaining testing apparatus, and training and testing animals. In addition, the Core seeks to develop ELISA based endocrine assay techniques for rapid determination of the reproductive phase of marmoset monkeys to support super-ovulation and transfection techniques 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. This project is ongoing. 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. -Effects of nasally administered oxytocin on FPS and visual social processing in differentially reared rhesus. summary: this project is evaluating dose responses and effects on fear-potentiated startle and social processing and memory using an eye tracking apparatus. Core Resources: core staff are responsible for all aspects of this study. -Development of double-perfusion brain harvesting technique. Summary: in collaboration with internal and external investigators, core staff has developed a method of harvesting brain that yields both fixed and fresh tissue. The procedure has been developed, and post-mortem validation is ongoing. Core Resources: core staff developed the procedure in-house, consulting with internal and external investigators when necessary. Four core animals were used while developing this process. Core staff handled all tissue processing and cutting before sending it for post-mortem analysis. -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

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICMH002902-07
Application #
8745788
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$12,711
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
Zip Code
Nelson, Eric E; Herman, Khalisa N; Barrett, Catherine E et al. (2009) Adverse rearing experiences enhance responding to both aversive and rewarding stimuli in juvenile rhesus monkeys. Biol Psychiatry 66:702-4
Barrett, Catherine E; Noble, Pamela; Hanson, Erin et al. (2009) Early adverse rearing experiences alter sleep-wake patterns and plasma cortisol levels in juvenile rhesus monkeys. Psychoneuroendocrinology 34:1029-40
Antoniadis, Elena A; Winslow, James T; Davis, Michael et al. (2009) The nonhuman primate amygdala is necessary for the acquisition but not the retention of fear-potentiated startle. Biol Psychiatry 65:241-8
Nelson, Eric E; Winslow, James T (2009) Non-human primates: model animals for developmental psychopathology. Neuropsychopharmacology 34:90-105
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
Davis, Michael; Antoniadis, Elena A; Amaral, David G et al. (2008) Acoustic startle reflex in rhesus monkeys: a review. Rev Neurosci 19:171-85
Winslow, James T; Noble, Pamela L; Davis, Michael (2008) AX+/BX- discrimination learning in the fear-potentiated startle paradigm in monkeys. Learn Mem 15:63-6