The primary long-range objective is to elucidate and characterize the actions of drugs of abuse as they influence and modify neuronal function. One of the crucial damaging aspects of drug addiction is the persistent wanting, or craving, that remains following rehabilitation that leads to relapse and a high failure rate in attempts to treat addiction. Because craving persists long after the cessation of withdrawal, and recovery from tolerance, it is often suggested that a drug-induced neural plasticity has occurred within the circuitry of the brain that sustains the potential for future triggering of drug craving. The neural underpinnings of the """"""""craving circuitry"""""""" of the brain are largely uncharacterized. The hippocampal formation is a region of the brain involved with memory formation and is crucial for the performance of several associative learning and memory tasks. The administration of addictive substances directly into the hippocampus has been shown to support self administration behavior, and the activation of this brain region can prime, or reinstate, drug seeking behavior in animal models of addiction. Investigating the role of the hippocampus in drug addiction is therefore a reasonable pursuit. Electrophysiological recording techniques will be used to monitor neuronal responses from the in vitro hippocampal slice preparation. The acute and persisting effects of cocaine applied either directly to the tissue slice or systemically via in viva injections prior to slice preparation are to be investigated. The central hypothesis of this proposal is the following: The neural adaptations resulting from exposure to drugs of abuse are likely to include modifications of normal synaptic plasticity mechanisms that are typically utilized to store information within neuronal networks. Thus an understanding of both the normal processes and the drug-induced changes are required to elucidate the long-term consequences of drug exposure. In this application, the mechanisms underlying the plasticity of synaptic plasticity (i.e. metaplasticity) in the hippocampal formation will be investigated, and the subsequent effects of exposure to cocaine on such processes will be assessed.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
3R01DA016302-05S1
Application #
7380953
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Sorensen, Roger
Project Start
2003-04-01
Project End
2008-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
5
Fiscal Year
2007
Total Cost
$83,300
Indirect Cost
Name
University of Georgia
Department
Physiology
Type
Schools of Veterinary Medicine
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
Keralapurath, Madhusudhanan M; Briggs, Sherri B; Wagner, John J (2017) Cocaine self-administration induces changes in synaptic transmission and plasticity in ventral hippocampus. Addict Biol 22:446-456
Scholpa, Natalie E; Briggs, Sherri B; Wagner, John J et al. (2016) Cyclin-Dependent Kinase Inhibitor 1a (p21) Modulates Response to Cocaine and Motivated Behaviors. J Pharmacol Exp Ther 357:56-65
Cummings, Brian S; Pati, Sumitra; Sahin, Serap et al. (2015) Differential effects of cocaine exposure on the abundance of phospholipid species in rat brain and blood. Drug Alcohol Depend 152:147-56
Keralapurath, Madhusudhanan M; Clark, Jason K; Hammond, Sherri et al. (2014) Cocaine- or stress-induced metaplasticity of LTP in the dorsal and ventral hippocampus. Hippocampus 24:577-90
Hammond, Sherri; Seymour, Claire M; Burger, Ashley et al. (2013) D-Serine facilitates the effectiveness of extinction to reduce drug-primed reinstatement of cocaine-induced conditioned place preference. Neuropharmacology 64:464-71
Hammond, Sherri; Wagner, John J (2013) The context dependency of extinction negates the effectiveness of cognitive enhancement to reduce cocaine-primed reinstatement. Behav Brain Res 252:444-9
Ha, Sangdeuk; Furukawa, Ruth; Stramiello, Michael et al. (2011) Transgenic mouse model for the formation of Hirano bodies. BMC Neurosci 12:97
Stramiello, Michael; Wagner, John J (2010) Cocaine enhancement of long-term potentiation in the CA1 region of rat hippocampus: lamina-specific mechanisms of action. Synapse 64:644-8
Kelamangalath, L; Wagner, J J (2010) D-serine treatment reduces cocaine-primed reinstatement in rats following extended access to cocaine self-administration. Neuroscience 169:1127-35
Kelamangalath, Lakshmi; Seymour, Claire M; Wagner, John J (2009) D-serine facilitates the effects of extinction to reduce cocaine-primed reinstatement of drug-seeking behavior. Neurobiol Learn Mem 92:544-51

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