Addiction has been a problem plaguing the world and has followed the United States into the 21st century. With little or no current effective pharmaco-treatments for cocaine abuse, addiction is a major area in need of investigation. A new field is beginning to evolve that evaluates the interactions of chemokines and drugs of abuse. Chemokines, currently being investigated in the realms of HIV and immunological processes, are also being evaluated to determine the interactive mechanisms with drugs such as cocaine and morphine. Clinical trials have begun to look at chemokines, their receptors and antagonists as potential targets for novel therapies. It has been shown that SDF-1a, (new nomenclature - CXCL12) causes a heterologous desensitization of opioid receptors. Preliminary data from this laboratory have shown that CXCL12 poteniates the behavioral activity of cocaine in rats. The hypothesis is that CXCL12 is interacting with dopaminergic neurons causing the increase in ambulatory and stereotypic activity. This proposal will seek to study the mechanistic interaction of cocaine and CXCL12.
Specific aim I will evaluate the behavioral interaction upon concomitant administration of CXCL12 and cocaine, specific aim II will use immunohistochemistry to determine the location of CXCL12 and its receptor CXCR4 within the adult rat brain and specific aim III will utilize in vivo microdialysis to investigate the effects of CXCL12 on dopamine and glutamate levels via high performance liquid chromatography (HPLC). ? ?
Within the current study of chemokines and their receptors, there has been novel research showing the interaction between CXCL12 and drugs abuse, in particular, cocaine. We have revealed that the pretreatment of CXCL12 before cocaine administration causes a large increase in locomotor activity in rats. The further evaluation of the interaction between CXCL12 and cocaine can help us better understand this mechanism of action, as well as further the understanding of CXCL12 and its receptor CXCR4, which is also an important component of HIV research. ? ? ?
| Trecki, Jordan; Brailoiu, G Cristina; Unterwald, Ellen M (2010) Localization of CXCR4 in the forebrain of the adult rat. Brain Res 1315:53-62 |
| Trecki, J; Unterwald, E M (2009) Modulation of cocaine-induced activity by intracerebral administration of CXCL12. Neuroscience 161:13-22 |
