PHARMACOLOGY FACULTY
Selected Publications
  • France CP, Li JX, Owens WA, Koek W, Toney GM, Daws LC. Reduced effectiveness of escitalopram in the forced swimming test is associated with increased serotonin clearance rate in food-restricted rats. Int J Neuropsychopharmacol. 2009 Jul;12(6):731-6.
  • Baganz NL, Horton RE, Calderon AS, Owens WA, Munn JL, Watts LT, Koldzic-Zivanovic N, Jeske NA, Koek W, Toney GM, Daws LC. Organic cation transporter 3: Keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice. Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18976-81.
  • Daws LC. Unfaithful neurotransmitter transporters: focus on serotonin uptake and implications for antidepressant efficacy. Pharmacol Ther. 2009 Jan;121(1):89-99.
  • Daws, LC and Toney GM. (2007) Voltammetric methods to study kinetics and mechanisms for serotonin clearance in vivo. In, Electrochemical Methods in Neuroscience, for Methods and New Frontiers in Neuroscience (Eds. Michael AC, Simon SA, and Nicolelis MAL). CRC Press. Pp63-81.
  • Williams JM, Owens WA, Turner GH, Saunders C, Dipace C, Blakely RD, France CP, Gore JC, Daws LC#, Avison MJ#, and Galli A#. (2007) Hypoinsulinemia regulates amphetamine-induced reverse transport of dopamine. Public Library of Science Biology 5(10):2369-2378. # contributed equally
  • Daws, L.C., Munn, J.L., Valdez, M.F., Frosto-Burke, T., and Hensler, J.G. (2007) Serotonin transporter function, but not expression, is dependent on brain derived neurotropic growth factor (BDNF): In vivo studies in BDNF-deficient mice. Journal of Neurochemistry 101:641-651.
  • Callaghan, P.D., Owens, W.A., Javors, M.A., Sanchez, T.A., Jones, D., Irvine, R.J., and Daws, L.C. (2007) In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated administration of p-methoxyamphetamine (PMA), but not 3,4-methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin transporter function. Journal of Neurochemistry 100:617-627.
  • Zhu, C-B., Steiner, J.A., Munn, J.L., Daws, L.C., Hewlett, W.A., and Blakely, R.D. (2007) Rapid stimulation of presynaptic serotonin transport by A3 adenosine receptors. Journal of Pharmacology and Experimental Therapeutics. 322:332-340.
  • Daws, L.C., Montañez, S., Munn, J.L., Owens, W.A., Baganz, N.L., Boyce-Rustay J.M., Millstein, R., Wiedholz, L.M., Murphy, D.L. and Holmes, A. (2006) Ethanol inhibits clearance of brain serotonin by a serotonin transporter independent mechanism. Journal of Neuroscience 26:6431-6438.
    **Research Highlight featured in August 2006 edition of Nature Reviews Neuroscience Vol 7:593, "Under the Influence" by Daniel McGowen, Ph.D.
  • Fog, J.U., Khoshbouei, H., Holy, M., Owens, W.A., Vaegter, C.B., Sen, N., Nikandrova, Y., McMahon, D.G., Colbran, R.J., Daws, L.C., Sitte, H.H., Javich, J.A., Galli, A. and Gether, U. (2006) Calmodulin kinase II interacts with the dopamine transporter C-terminus to regulate amphetamine-induced reverse transport. Neuron 51(4):417-429.
Lynette C. Daws
 

Lynette C. Daws

Professor of Physiology and Pharmacology
Ph.D. Flinders University of South Australia

Office: 210-567-4361
Email: daws@uthscsa.edu

 

View video introduction to Dr. Daws' lab

 

Keywords

Serotonin transporter, dopamine transporter, depression, stress, drug abuse, in vivo chronoamperometry

 

Research Summary

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.

 

Daws lab group photos

 

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).