One of the major determinants of reinstatement of cocaine use among human addicts is acute re-exposure to the drug, which often precipitates cocaine craving and relapse. This grant proposal will use an animal model of cocaine relapse in order to determine the anatomical and pharmacological determinants of the reinstatement of cocaine seeking. Specifically, these aims will systematically analyze ionotropic glutamate receptors in the core and shell subregions of the nucleus accumbens and their respective roles in reinstatement.
Specific Aim 1 will assess the ability of intra-accumbal core or shell AMPA to reinstate cocaine-seeking. We will then determine the influence intra-accumbal core or shell microinjection of an AMPA receptor antagonist has on the reinstatement of cocaine priming-induced drug seeking.
Specific Aim 2 will methodically analyze the effects of NMDA agonists and antagonists administered into either the core or the shell of the nucleus accumbens on the reinstatement of cocaine-seeking. It is possible that reinstatement induced by intra-accumbal AMPA, NMDA, or an NMDA antagonist could be dopamine-dependent, a hypothesis that will be addressed in Specific Aim 3.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DA019304-02
Application #
7072352
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2005-07-01
Project End
2010-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$46,201
Indirect Cost
Name
Boston University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Yee, Judy; Famous, Katie R; Hopkins, Thomas J et al. (2011) Muscarinic acetylcholine receptors in the nucleus accumbens core and shell contribute to cocaine priming-induced reinstatement of drug seeking. Eur J Pharmacol 650:596-604
Sadri-Vakili, Ghazaleh; Kumaresan, Vidhya; Schmidt, Heath D et al. (2010) Cocaine-induced chromatin remodeling increases brain-derived neurotrophic factor transcription in the rat medial prefrontal cortex, which alters the reinforcing efficacy of cocaine. J Neurosci 30:11735-44
Schmidt, Heath D; Famous, Katie R; Pierce, R C (2009) The limbic circuitry underlying cocaine seeking encompasses the PPTg/LDT. Eur J Neurosci 30:1358-69
Kumaresan, Vidhya; Yuan, Menglu; Yee, Judy et al. (2009) Metabotropic glutamate receptor 5 (mGluR5) antagonists attenuate cocaine priming- and cue-induced reinstatement of cocaine seeking. Behav Brain Res 202:238-44
Vassoler, Fair M; Schmidt, Heath D; Gerard, Mary E et al. (2008) Deep brain stimulation of the nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug seeking in rats. J Neurosci 28:8735-9
Famous, Katie R; Kumaresan, Vidhya; Sadri-Vakili, Ghazaleh et al. (2008) Phosphorylation-dependent trafficking of GluR2-containing AMPA receptors in the nucleus accumbens plays a critical role in the reinstatement of cocaine seeking. J Neurosci 28:11061-70
Anderson, Sharon M; Famous, Katie R; Sadri-Vakili, Ghazaleh et al. (2008) CaMKII: a biochemical bridge linking accumbens dopamine and glutamate systems in cocaine seeking. Nat Neurosci 11:344-53
Famous, Katie R; Schmidt, Heath D; Pierce, R Christopher (2007) When administered into the nucleus accumbens core or shell, the NMDA receptor antagonist AP-5 reinstates cocaine-seeking behavior in the rat. Neurosci Lett 420:169-73
Schmidt, Heath D; Anderson, Sharon M; Famous, Katie R et al. (2005) Anatomy and pharmacology of cocaine priming-induced reinstatement of drug seeking. Eur J Pharmacol 526:65-76