The broad area of my research is studying the function and regulation of biogenic amine transporters, including the classical serotonin, dopamine and norepinephrine transporters, as well as more recently identified transporters in brain, such as the organic cation transporters and plasma membrane monoamine transporter. Understanding how these transporters function is important in that they are pivotal in controlling the extracellular concentration of biogenic amines and hence, neurotransmission. Moreover, they are the primary site of action for numerous psychotherapeutic and addictive drugs.
One of my primary research interests relates to the serotonin transporter. In humans, a polymorphism of the gene encoding the serotonin transporter leads to its reduced expression. This polymorphism has been linked to a number of disorders including alcoholism and depression. Moreover, individuals with this polymorphism appear to respond differently to drug treatment. We are using mice with a genetically induced reduction in the density of the serotonin transporter (heterozygote serotonin transporter knockout mice, which express 50% fewer serotonin transporters than the "normal", wild-type mouse) to investigate neuroadaptive changes associated with reduced expression of the transporter. We are further investigating the interaction that occurs between stress, serotonin transporter genotype and predisposition to depression and alcoholism, as well as resistance to commonly prescribed medications for these disorders.
Another major focus of our studies is the mechanism of MDMA ("Ecstasy"), para-methoxyamphetamine, amphetamine and cocaine at the dopamine and serotonin transporters. The acute and long term effects of these drugs on transporter function in vivo are being studied. In addition, we have more recently demonstrated that hormones, such as insulin, can influence the activity of biogenic amine transporters. Importantly, we have found that insulin status dictates responsiveness to certain drugs of abuse as well as antidepressants. Thus, it appears that insulin can profoundly affect reward and mood circuitry in brain. We are currently investigating the mechanism through which this occurs. These data have important implications for understanding the high-comorbidity of depression, eating disorders and drug abuse as well as food "addictions," which may lead to obesity.
On a more fundamental level, we are interested in studying how biogenic amine transporters are regulated by receptors. We are currently investigating the role of the 5-HT1B autoreceptor, alpha-adrenoceptors, adenosine receptors and interleukin1-b receptors in regulating activity of the serotonin transporter and of the D2 autoreceptor in regulating activity of the dopamine transporter.
We implement several state-of-the-art techniques including in vivo high-speed chronoamperometry as well as a variety of neurochemical, molecular and behavioral approaches. Dr. Daws' research group comprises Dr. Georgianna Gould (Assistant Professor/Research), W. Anthony Owens (Senior Research Associate), Rebecca Horton (Research Associate), Melissa Vitela (Senior Research Associate), and Deana Apple (Graduate Student).
We implement several state-of-the-art techniques including in vivo high-speed chronoamperometry as well as a variety of neurochemical, molecular and behavioral approaches. Dr. Daws' research group comprises Dr. Georgianna Gould (Assistant Professor/Research), W. Anthony Owens (Senior Research Associate), Melissa Vitela (Senior Research Associate), Corey Smolik (Research Assistant with Dr. Gould), Dr. Rheaclare Fraser (Postdoctoral Fellow) and Nathan Mitchell (Graduate Student).
Key Words: Serotonin Transporter; Dopamine Transporter; Norepinephrine Transporter, Organic Cation Transporters, Depression; Stress; Drug Abuse; In Vivo Chronoamperometry