Lynette C. Daws
Professor of Physiology and Pharmacology
Ph.D. Flinders University of South Australia
Serotonin transporter, dopamine transporter, depression, stress, drug abuse, in vivo chronoamperometry
The broad area of my research is studying the function and regulation of biogenic amine transporters (the serotonin, dopamine and norepinephrine transporters). 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 alcoholism.
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 the dopamine transporter. Importantly, we have found that insulin status dictates responsiveness to certain drugs of abuse. Thus, it appears that insulin can profoundly affect dopamine reward circuitry in brain. We are currently investigating the mechanism through which this occurs. These data have important implications for understanding the high-comorbidity of 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-HT 1B autoreceptor, alpha-adrenoceptors and adenosine 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 molecular and behavioral approaches. Dr. Daws' research group comprises Dr. Georgianna Gould (Assistant Professor/Research), W. Anthony Owens (Research Associate), Rebecca Horton and Steven Alvarado (Senior Research Assistants), and Nicole Baganz and Pete Campos (Graduate Students).