This ADAMHA RSDA renewal application (Level II) will support an investigator working on the neurobiological basis of learning and memory. This research program focuses on neurochemical regulation of these functions in limbic system structures. One major goal of this work is to examine the organization of limbic opioid peptides and their relation to other systems that innervate the forebrain (ascending norepinephrine pathways and the basal forebrain cholinergic (ACh) system). In a series of experiments a special emphasis is placed on assessing opioid peptide regulation of the septo-hippocampal ACh pathway (PART II). In this context complementary experiments are also designed to assess the effects of aging on both behavior and the function of these neurochemical systems, i.e. ACh and opioid peptide (PART IV). A second major theme of this work is to determine the principles that govern the activity of opioid peptides. Behavioral experiments (PART I) are designed to further analyze the training conditions that exhibit sensitivity to opiate antagonist treatments. Using classical conditioning procedures (overshadowing and conditioned inhibition) these experiments are designed to make contact with research linking opioid peptide function to mechanisms of attention. In PART III the effects of selected training procedures on opioid peptide content/activity in limbic structures (amygdala and hippocampus) will be examined. The goals of this program are to provide information about the neurochemical systems that underly normal learning and memory processes and to provide a basis for the development of treatment strategies for clinical conditions characterized by a deterioration in these capacities. Further plans for collaboration and extended training with other neuroscientists at the applicant's institution and at NIEHS (National Institute of Environmental Health Sciences), and a proposed visit to another major laboratory are included in the application.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
2K02MH000406-06
Application #
3069757
Study Section
Research Scientist Development Review Committee (MHK)
Project Start
1982-07-01
Project End
1992-06-30
Budget Start
1987-08-01
Budget End
1988-06-30
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Arts and Sciences
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Holland, P C; Gallagher, M (1993) Amygdala central nucleus lesions disrupt increments, but not decrements, in conditioned stimulus processing. Behav Neurosci 107:246-53
Holland, P C; Gallagher, M (1993) Effects of amygdala central nucleus lesions on blocking and unblocking. Behav Neurosci 107:235-45
Gallagher, M; Holland, P C (1992) Preserved configural learning and spatial learning impairment in rats with hippocampal damage. Hippocampus 2:81-8
Hatfield, T; Graham, P W; Gallagher, M (1992) Taste-potentiated odor aversion learning: role of the amygdaloid basolateral complex and central nucleus. Behav Neurosci 106:286-93
Willner, J; Gallagher, M; Graham, P W et al. (1992) N-methyl-D-aspartate antagonist D-APV selectively disrupts taste-potentiated odor aversion learning. Behav Neurosci 106:315-23
Gallagher, M; Graham, P W; Holland, P C (1990) The amygdala central nucleus and appetitive Pavlovian conditioning: lesions impair one class of conditioned behavior. J Neurosci 10:1906-11
Gallagher, M; Burwell, R D (1989) Relationship of age-related decline across several behavioral domains. Neurobiol Aging 10:691-708
Jiang, H K; Owyang, V V; Hong, J S et al. (1989) Elevated dynorphin in the hippocampal formation of aged rats: relation to cognitive impairment on a spatial learning task. Proc Natl Acad Sci U S A 86:2948-51
Gallagher, M; Pelleymounter, M A (1988) An age-related spatial learning deficit: choline uptake distinguishes ""impaired"" and ""unimpaired"" rats. Neurobiol Aging 9:363-9
Decker, M W; Pelleymounter, M A; Gallagher, M (1988) Effects of training on a spatial memory task on high affinity choline uptake in hippocampus and cortex in young adult and aged rats. J Neurosci 8:90-9

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