Both memory and addiction produce long-lasting changes in behavior and result in chronic neural adaptations in response to repeated neural activity. It is therefore likely that memory and addiction recruit some of the same molecular mechanisms of synaptic plasticity in the same neural structures. In the present proposal, we explore the parallels between addiction and memory by examining the impact of genetic and anatomical manipulations known to affect memory on addiction-related behavioral plasticity. In a simple behavioral paradigm in mice we can rapidly quantify psychomotor sensitization to repeated cocaine injections, as well as the conditioned response to cues associated with cocaine administration, the contextual control over the expression of cocaine sensitization, and conditioned place preference induced by cocaine. First, we use this paradigm to evaluate the role of the hippocampus and amygdala in addiction-related memory. Second, we use inducible and region-specific disruption of calcium/calmodulin- dependent protein kinase II (CaMKII), a criticial kinase in memory formation, in addiction. Finally, we examine the role of calcium calmodulin in addiction. A benefit of using modern genetic manipulation is the ability to better localize key neuroadaptations through disruption of dendritic translation, and inducible region-specific disruption of alpha-CaMKI in the forebrain and striatum. The inducible and reversible molecular manipulations we propose, post-induction disruption of CaMKII or calcium calmodulin, actually have the potential to reverse sensitization to cocaine and related memories. Taken together, these studies will evaluate the parallels between memory and addiction-related behavioral plasticity and shed considerable light on whether manipulations of memory will prove useful in the treatment of addiction.Project Narrative Addiction is a major social and medical problem affecting millions of compulsive drug users. In the present proposal we examine the relationship between memory and addiction at the level of the brain. If memory and addiction prove to be highly related, disruptions of memory may prove highly useful in the treatment of addiction. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA020041-01A2
Application #
7373971
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Pilotte, Nancy S
Project Start
2007-09-30
Project End
2012-06-30
Budget Start
2007-09-30
Budget End
2008-06-30
Support Year
1
Fiscal Year
2007
Total Cost
$291,974
Indirect Cost
Name
University of California San Diego
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Carmack, Stephanie A; Howell, Kristin K; Rasaei, Kleou et al. (2014) Animal model of methylphenidate's long-term memory-enhancing effects. Learn Mem 21:82-9
Wood, Suzanne; Sage, Jennifer R; Shuman, Tristan et al. (2014) Psychostimulants and cognition: a continuum of behavioral and cognitive activation. Pharmacol Rev 66:193-221
Howell, Kristin K; Monk, Bradley R; Carmack, Stephanie A et al. (2014) Inhibition of PKC disrupts addiction-related memory. Front Behav Neurosci 8:70
Carmack, Stephanie A; Kim, Jeesun S; Sage, Jennifer R et al. (2013) The competitive NMDA receptor antagonist CPP disrupts cocaine-induced conditioned place preference, but spares behavioral sensitization. Behav Brain Res 239:155-63
Shuman, Tristan; Cai, Denise J; Sage, Jennifer R et al. (2012) Interactions between modafinil and cocaine during the induction of conditioned place preference and locomotor sensitization in mice: implications for addiction. Behav Brain Res 235:105-12
Carmack, Stephanie A; Wood, Suzanne C; Anagnostaras, Stephan G (2010) Amphetamine and extinction of cued fear. Neurosci Lett 468:18-22
Shuman, Tristan; Wood, Suzanne C; Anagnostaras, Stephan G (2009) Modafinil and memory: effects of modafinil on Morris water maze learning and Pavlovian fear conditioning. Behav Neurosci 123:257-66
Wood, Suzanne C; Anagnostaras, Stephan G (2009) Memory and psychostimulants: modulation of Pavlovian fear conditioning by amphetamine in C57BL/6 mice. Psychopharmacology (Berl) 202:197-206