Drug addiction is an immense medical and social problem worldwide. A central focus of current research is elucidating the long-term molecular and cellular alterations in the mesolimbic system that subserve addiction. Neurochemical, electrophysiological and behavioral studies have highlighted an important role for alterations in the glutamatergic system in this process. However the molecular mechanisms mediating these changes are unclear. Recent studies have identified Narp as an immediate early gene involved in clustering AMPA receptor subunits at synaptic sites. Narp, therefore, could be contributing to alterations in excitatory transmission induced by neuronal stimulation. In preliminary studies we found that Narp expression is induced in the ventral tegmantal area (VTA) with chronic cocaine administration and may therefore play an important role in mediating alterations in glutamatergic transmission induced by drugs of abuse. As an initial step in investigating its role, we plan to: (A) Determine key aspects of Narp regulation by drugs of abuse. In particular, we shall define the time course and regional distribution of Narp expression following cocaine administration, and assess whether Narp expression is also altered by other drugs of abuse. (B) Develop methods to manipulate expression of Narp in the VTA using the herpes simplex virus vector system.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Small Research Grants (R03)
Project #
5R03DA014063-02
Application #
6515863
Study Section
Special Emphasis Panel (ZRG1-MDCN-4 (02))
Program Officer
Colvis, Christine
Project Start
2001-04-01
Project End
2003-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
2
Fiscal Year
2002
Total Cost
$81,750
Indirect Cost
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Zal, Tomasz; Gascoigne, Nicholas R J (2004) Photobleaching-corrected FRET efficiency imaging of live cells. Biophys J 86:3923-39
Reti, Irving M; Baraban, Jay M (2003) Opiate withdrawal induces Narp in the extended amygdala. Neuropsychopharmacology 28:1606-13
Reti, Irving M; Minor, Lloyd B; Baraban, Jay M (2002) Prominent expression of Narp in central vestibular pathways: selective effect of labyrinth ablation. Eur J Neurosci 16:1949-58
Reti, Irving M; Reddy, Radhika; Worley, Paul F et al. (2002) Selective expression of Narp, a secreted neuronal pentraxin, in orexin neurons. J Neurochem 82:1561-5