F A C U L T Y P R O F I L E
HEN, RENE, PH.D.
SEROTONIN RECEPTORS AND BEHAVIOR
Office: Lawrence C. Kolb Research Building | 7th Floor | Room 767
Serotonin (5HT) is involved in a wide range of behaviors, and serotonergic drugs are used in the treatment of a number of pathological states such as depression, appetite disorders, and migraines. Pharmacological studies and molecular cloning have identified several subtypes of receptors with distinct pharmacological properties, signaling systems, and tissue distributions.
The study of the function of individual serotonin receptor subtypes has been hampered by the lack of specific drugs. In addition, a number of the serotonergic drugs that are active in the treatment of neuropsychiatric disorders influence the whole serotonergic system. For example, antidepressants such as fluoxetine (Prozac) are 5-HT uptake blockers. These drugs presumably potentiate the action of 5-HT at multiple post-synaptic sites. We do not know which of these post-synaptic receptors are responsible for the antidepressant activities of 5-HT uptake blockers, however.
To dissect the contributions of individual serotonin receptors to physiology and behavior, we have created mouse mutants lacking individual receptor subtypes. These mice provide genetic models for a number of human behavioral traits such as: impulsiveness, depression, and vulnerability to drugs of abuse. The neural circuits underlying these traits are currently under investigation.
1. Hen, R. (1996) Mean Genes Neuron 16:17-21
2. Ramboz, S., Oosting, R., Ait Amara, D., Kung, Blier, P., Mendelsohn, M., Mann, J. Brunner, D. and Hen, R. (1998) 5-HT1A receptor knockout: an animal model of anxiety-related disorder. Proc. Natl. Acad. Sci. USA 95:14476-14481.
3. Yamamoto, A., Lucas, J. J., and Hen, R. (2000) Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease Cell 101:57-66.
4. Santarelli, L., Gobbi, G., Debs, P., Sibille, E., Blier, P., Hen, R., and Heath, M. (2001) Genetic and pharmacological disruption of neurokinin 1 receptor function decreases anxiety- related behaviors and increases serotonergic function. Proc. Natl. Acad. Sci. USA. 98:1912-1917
5. Gross, C., Zhuang, X., Stark, K., Ramboz, S., Oosting, R., Kirby, L., Beck, S., and Hen, R. (2002) Serotonin1A receptor is required during development to establish normal emotional behavior Nature 416:396-400
6. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R. (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants Science 301(5634):805-9
7. Doetsch F, Hen R (2005) Young and excitable: the function of new neurons in the adult mammalian brain Curr Opin Neurobiol 15(1) Review:121-8
8. Gordon JA, Lacefield CO, Kentros CG, Hen R (2005) State-dependent alterations in hippocampal oscillations in serotonin 1A receptor-deficient mice J Neurosci 25(28):6509-19