Elucidating long-term neurochemical changes in the brain after chronic cocaine use is a main focus of addiction research. The neurotransmitters dopamine and glutamate and their receptors are highly affected by cocaine use and abuse. In this project we will examine the localization of metabotropic glutamate receptors (mGluRs) in the nucleus accumbens (NA), an area in the brain that is involved in experiencing reward to natural substances such as food & water, but also to drugs of abuse. Recent studies demonstrate that mGluRs are essential to mediate self-administration of cocaine in rodents. We therefore propose to use high resolution electron microscopic techniques to study the localization of these receptors in the NA of normal animals, in animals treated with cocaine and animals genetically manipulated to no longer express proteins that control the trafficking of these glutamate receptors in neurons. Findings from this project could lead to a better understanding of changes in the brain that accompany cocaine use and leads an individual vulnerable to addiction. This project will also provide valuable training for me to become a conscientious scientist and pave the way for a successful postdoctoral formation in neuroanatomy & neuropharmacology. ? ? ?
Mitrano, D A; Pare, J-F; Smith, Y (2010) Ultrastructural relationships between cortical, thalamic, and amygdala glutamatergic inputs and group I metabotropic glutamate receptors in the rat accumbens. J Comp Neurol 518:1315-29 |
Mitrano, D A; Arnold, C; Smith, Y (2008) Subcellular and subsynaptic localization of group I metabotropic glutamate receptors in the nucleus accumbens of cocaine-treated rats. Neuroscience 154:653-66 |