Self-Administration Chambers

The Neuroimaging Research Branch (NRB) needs purchase additional self-administration training apparatuses/chambers
which are used to train laboratory rats to self-administer compounds such as methamphetamine. These are needed to ensure enough apparatuses are available to complete the project.

NRB previously found that years of cocaine use alter human brain activity using the non-invasive imaging technique
called functional Magnetic Resonance Imaging (fMRI). In addition, NRB found similar changes in the rat brain, particularly in regions called the prelimbic cortex and orbitofrontal cortex after weeks of methamphetamine intake. However, it is
not clear whether dysfunction of these brain regions are responsible for uncontrolled drug seeking found in addicted users. To shed light on this issue, we propose to use the genetic, viral technology called Designer Receptors Exclusively Activated by Designer Drugs (DREADDS), which allows us to temporarily suppress and stimulate these brain regions with injections of
laboratory-made chemicals, and we apply this technology in a rat model of methamphetamine self-administration.

In addition, we will monitor changes in rat brain activity using fMRI. fMRI allows us to investigate regional brain activity and interactions between different cellular networks in the brain. We hypothesize that changes in the connectivity of the
prefrontal and orbitofrontal cortex are associated with increased motivation to seek and take drugs of abuse, and that stimulating or suppressing these regions can affect that motivation. This is based on our previous findings that these the connectivity of these regions changes after chronic and increasingly compulsive methamphetamine self-administration. The proposed research may help to understand brain mechanisms responsible for compulsive drug use.