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 several major projects in the laboratory currently:

1. 5-HT1B autoreceptors in stress related behaviors. 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 are also interested in the contribution of several other key proteins to serotonergic neuron function, including 5HT1A receptors, serotonin transporter, and tryptophan hydroxylase 2 as well as interactions between these neurons and other neurotransmitter systems.

2. Tryptophan Hydoxylase-2. We have found this enzyme, the rate limiting regulator of serotonin biosynthesis, to be regulated by estrogen and stress exposure. We are currently investigating how molecular manipulations of its expression will alter behavior and physiology.

3. 5-HT1B and 5-HT6 receptors in drug reward mechanisms. Nucleus accumbens neurons express these receptors heavily, and manipulating their expression with targeted gene transfer alters the rewarding properties of cocaine, amphetamine, and alcohol. We are continuing to evaluate the potential of these receptors to be targets for manipulating the addictive properties of these drugs. 4. 5-HT6 receptors in cognition. Using several behavioral models, we have found that 5-HT6 antagonists enhance memory and overexpression of 5-HT6 receptors in striatum impairs learning. The mechanism for these cognitive effects is not known but likely involves the modulation of other neurotransmitter systems, especially acetylcholine.