My laboratory is studying the regulation of serotonin receptors in rat brain in animal models of psychiatric illnesses. We use techniques that span molecular to behavioral levels of analysis. Our strategy is to explore the reciprocal relationship between receptor expression and behavior using techniques that focus on discrete brain regions. There are currently three main projects in the laboratory:
1. The role of 5-HT1B autoreceptors in stress related behaviors associated with stress and depression. We use viral mediated gene transfer to manipulate 5-HT1B expression in clusters of serotonergic neurons that project to different brain regions and determine the behavioral and physiological outcomes. We have been focusing recently on how these autoreceptors regulate serotonin transporter function using electrochemical and biochemical assays. We are now adapting these methods to transgenic mice that conditionally express 5-HT1B receptors.
2. The role of 5-HT1B and 5-HT6 receptors in drug reward mechanisms. Nucleus accumbens and dorsal striatum neurons express these receptors heavily, and manipulating their expression with targeted gene transfer alters the rewarding properties of cocaine, amphetamine, and alcohol. We are manipulating these receptors using RNAi (knockdown) or overexpression constructs in pathway-specific viral vectors and measuring the resulting changes in addictive-like behavior using operant conditioning, cocaine self-administration, and other.
3. Novel receptors to manipulate brain function. We are using light activated receptors and DREADD receptors in combination with pathway-specific viral vectors to study how specific groups of neurons participate in complex emotional behaviors relating to stress and addiction.