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Drug Effects on Learning and Memory

$359,764R01FY2006MHNIH

University Of California-Irvine, Irvine CA

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Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): The overall objective of this research program is to understand the neurobiological systems regulating the consolidation of long-term memory. Previous research has shown that stress hormones and activation of the amygdala enhance the consolidation of recent experiences. Such evidence suggests that the amygdala regulates the strength of memory in relation to the significance of experiences. The specific aims of the experiments are to determine: 1) neuromodulatory interactions within the basolateral region of the amygdala (BLA) that are critically involved in regulating memory consolidation, 2) BLA regulation of the consolidation of different aspects or forms of memory, and 3) BLA influences on other brain regions involved in consolidation of different aspects or forms of memory. Experiments will use intra-BLA infusions administered to rats after inhibitory avoidance training to test the specific hypothesis that muscarinic cholinergic activation in the BLA is critical for the effects, on memory consolidation, of drugs affecting other neuromodulatory systems, including noradrenergic and GABAergic systems. Experiments will also use in vivo microdialysis and high performance liquid chromatography to determine the effects of inhibitory avoidance training on the release of norepinephrine and acetyicholine in the BLA. Other experiments will use intra-BLA infusions of memory-enhancing doses of noradrenergic and muscarinic cholinergic drugs administered after either context exposure or a brief footshock to determine whether the infusions differentially affect memory for the context or shock experiences. Experiments using intra-BLA drug infusions administered after exposure to context or footshock will determine BLA influences on memory processing in other brain regions. The findings of these experiments will significantly increase our understanding of the functioning of BLA activation in regulating the consolidation of long-term memory. Additionally, as the BLA mediates stress hormone-induced enhancement of memory consolidation, the findings may have important implications for understanding and treating disorders of emotionally influenced memory.

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