Drug addiction, including to amphetamines and their derivatives, cost the United States approximately $181 billion each year. Unfortunately, the molecular basis for drug seeking behaviors and addiction is still quite poorly understood and much remains to be studied. Therefore, novel therapeutic treatments for drug addiction, especially for amphetamines, must be identified and tested. In order to do this, a better understanding of the brain regions and cell types involved in this phenomenon is necessary. Recent exciting research has established that some behavioral phenotypes are controlled by the CB1 receptors in the context of addiction- related behaviors. These receptors are expressed at high levels on the GABAergic medium spiny neurons (MSNs). The goal of this NRSA is to better understand how the CB1 receptors expressed on MSNs contribute to the behavioral phenotypes observed after amphetamine sensitization and conditioned place preference. This will be accomplished by validating, in Specific Aim 1, our viral strategy to deliver CB1 receptors specifically to MSNs in the direct or indirect pathway.
In Specific Aim 2, the contribution of diret or indirect MSNs to amphetamine sensitization and conditioned place preference will be determined. In addition, the molecular correlates of amphetamine sensitization will also be examined. Together, the Aims of this study will directly assess how CB1 receptors on MSNs contribute to the behavioral responses to amphetamine.
Despite decades of research, the molecular basis for drug addiction is still poorly understood. Therefore, understanding the distinctive aspects of how amphetamine administration affects neuronal function and how cannabinoid CB1 receptors participate in this response can help develop new treatments which, in turn, can lead to better clinical outcomes and therapies for these patients.