Opiate manipulations in the amygdala complex alter learning and memory processes when aversive conditioning tasks are used. Current research in our laboratory is examining opiate/norepinephrine (NE) interactions in the regulation of learning and memory of aversive conditioning. At the same time, numerous investigations have reported that systemic opiate agonist and antagonist administration can alter memory using a variety of tasks which employ aversive, appetitive and non-reinforced exposure to stimuli. A major goal of the proposed research will be to explore neural systems and mechanisms which may underlie the effects of opiate treatment on memory for non-aversive experiences. The behavioral tasks which have been recently employed in our laboratory include: 1) a latent inhibition paradigm in which retention of CS pre-exposure is assessed on subsequent classical conditioning of heart rate responses in rabbits and 2) a food-rewarded spatial learning task using rats. The results of our preliminary studies indicate that in both of these tasks post-training systemic administration of an opiate antagonist enhances retention, an effect which parallels that obtained using aversive conditioning procedures. In the proposed experiments, the amygdala complex and the hippocampal formation will be explored as possible target sites for the effects of opiates on memory when these non-aversive tasks are used. In addition we propose to investigate whether the effects of opiate manipulation on memory using these tasks are dependent on intact NE function in the brain. These experiments should provide important new information regarding the distribution and function of brain opioid peptides which regulate memory processes. Other experiments in this proposal are included to develop an in vitro amygdala slice preparation from rabbit brain which will include the central nucleus and several of its inputs. The central nucleus appears to be a critical component of the neural circuitry which underlies the acquisition of classically conditioned heart rate in the rabbit. This in vitro preparation may provide a valuable tool for investigating synaptic processing in this region which may lead to new insights into neural mechanisms involved in learning and memory.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH035554-06
Application #
3375707
Study Section
(BPNB)
Project Start
1980-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
6
Fiscal Year
1985
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
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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
Holland, P C (1993) Cognitive aspects of classical conditioning. Curr Opin Neurobiol 3:230-6
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
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

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