The goals of this project will be to clarify the molecular biology and neuroanatomy of brain opioid systems by studying enkephalin convertase (EC), a recently discovered enzyme in the processing pathway for opiate peptides. Opioid systems in the brain participate in the regulation of mood and affect, control of the autonomic nervous system, and the pathophysiology of neuropsychiatric conditions, such as Huntington's disease, Alzheimer's disease, and Parkinson's disease.
The first aim will be to map EC and EC mRNA in rat brain and in the periphery using immunohistochemistry and in situ hybridization. Double label studies will investigate the colocalization of EC with opioid and non opioid peptides. Combined retrograde tracer plus immunohistochemical techniques will permit the tracing of EC containing pathways in brain, particularly in areas of the hindbrain involved in cardiovascular regulation, and in areas of the limbic system which may be involved with the action of ECT or antidepressant drugs.
The second aim will be to study the regulation of EC in brain, pituitary and adrenal, with manipulations such as insulin or dexamethasome treatment, morphine dependence, or antidepressant treatment. EC enzyme activity, EC immunoreactivity, and EC mRNA levels will be studied coordinately.
The final aim will be to define the neuropathology of human opioid systems in neuropsychiatric illnesses, such as Huntington's disease, Parkinson's disease, and Alzheimer's disease. Sections through the amygdala, areas of basal ganglia, and selected brainstem regions in patients brains will be labeled immunocytochemically for EC and compared with controls. These studies should clarify the neuroanatomy and molecular biology of brain opioid systems and their role in the pathophysiology of neuropsychiatric illness.
