The role of Serotonergic systems in mood regulation

Research interests

The long-term goal of my research is to understand the role of serotonergic systems on mood regulation and on etiology and therapy of psychiatric disorders. Serotonin (5-HT) is an important neurotransmitter.  It has been known that 5-HT is involved in the regulation of emotion. Alteration in the function of serotonergic system may be related to etiology of affective disorders. Furthermore, several serotonin agents have been used to treat psychiatric disorders.  However, the mechanisms underlying the effect of 5-HT on mood regulation are still unclear.  Understanding these mechanisms will have significant impact in development of better therapeutic approaches for psychiatric disorders.  Currently, my research projects focus on:

1) Role of 5-HT1A and 5-HT2C receptors on anxiety behaviors and stress response.  5-HT1A and 5-HT2C receptors have known to play a role in anxiety behaviors.  5-HT1A receptors are also involved in the inhibition of stress response.  Our research is to determine the neuron-circuitries and cellular and molecular mechanisms underlying these regulations.  The recombinant-adenovirus technique is used to manipulate expression of 5-HT1A or 5-HT2C receptors in the specific neurons in the selected brain regions of mice.

2) We have previously found that 5-HT transporter (SERT) knockout mice are more sensitive to stress, which is consistent with the observation in the human who carries short allele of 5-HT transporter-linked promoter region polymorphism (5-HTTLPR).  Our recent studies indicate that the hypothalamus-pituitary-adrenal axis (HPA axis) is impaired in SERT knockout, which could be related to the increased sensitivity to stress in these mice.  We are currently studying the mechanisms underlying the alterations in the HPA axis in SERT knockout mice. The outcomes of these projects will have significant impact on understanding the etiology of serotonin-related anxiety and in contributing to the development of better therapeutic approaches for anxiety disorders.

Selected publications:

• Li, Q., Wichems, C., Heils, A., Van de Kar, L.D., Lesch, K.P. and Murphy, D.L.  Reduction of 5-HT1A-Mediated  Temperature and Neuroendocrine Responses and 5-HT1A Binding Sites in 5-HT transporter Knockout Mice.  J. Pharmacol. Exp. Ther.  291:999-1007; 1999.

• Li, Q., Wichems, C., Heils, A., Lesch, K.P. and Murphy, D.L.  Reduction in the density and expression, but not G protein coupling, of 5-HT1A receptors in 5-HT transporter knockout mice: gender and brain region differences.  Journal of Neuroscience.  20:7888-7895; 2000.

• Murphy, D.L., Li, Q., Engel, S., Wichems, C., Andrews, A., Lesch, K.P., and Uhl, G.  Genetic perspectives on the serotonin transporter.  Brain Research Bulletin.  56:487-494; 2001.

• Li, Q., Wichems, C. M., Ma, L., Van de Kar L.D., Garcia F., and Murphy D.L.  Brain-region specific alterations of 5-HT2A and 5-HT2C receptors in 5-HT transporter knockout mice.  J. Neurochemistry.  84:1256-1265; 2003.

• Li, Q., Holmes, A., Ma, L., Van de Kar, L.D., Garcia, F., and Murphy, D.L.  Medial hypothalamic 5-HT1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: Application of recombinant adenovirus containing 5-HT1A sequences.J.Neurosci.  24, 10868-10877, 2004.

• Li, Q.  Cellular and molecular alterations in mice with deficient and reduced serotonin transporters. Molecular Neurobiology.  34(3): 51, 2006.