Neuroscience Graduate Program at UCSF
Studying Drugs of Abuse in Drosophila
Drug abuse is one of the most devastating social and medical problems in our society, yet little is known about the mechanisms by which these drugs regulate behavior. Our laboratory is using the fruitfly Drosophila, with its accessibility to genetic and molecular analysis, to help establish the missing links between genes and drug-induced behaviors.
Flies display many of the behaviors observed in mammals after both, acute and chronic exposure to ethanol. Flies display signs of hyperactivity, incoordination, followed by sedation and hypnosis. In addition, flies develop tolerance to ethanol and undergo 'withdrawal-like' symptoms upon ethanol removal. We have developed assays that allow the quantification of these behaviors and have isolated mutants that respond abnormally to ethanol exposure. For example, mutations in the neuropeptide gene amnesiac are overly sensitive to the sedative effects of ethanol when measured in the inebriometer. We are using similar approaches to study the mechanisms that regulate the responses to psychostimulants such as cocaine and nicotine.In addition to defining drug-induced behaviors and their genetic control, we have begun to map the neuroanatomical sites of drug action and their relation to specific behaviors. For this purpose we are using targeted expression of tetanus toxin light chain, which cleaves synaptobrevin and thus eliminates synaptic transmission, in specific brain regions. We are not only interested in defining these brain regions, but also in studying their development. Integrating the information gained from behavioral, genetic, molecular, and neuroanatomical analyses will help us gain an understanding of drug-induced behaviors.
Reza Azanchi, Lab Manager
Karen Berger, Senior Research Scientist
Anita Devineni, Graduate Student
Mark Eddison, Postdoctoral Fellow
Ryan Joseph, Graduate Student
David Kapfhamer, Postdoctoral Fellow
Karla Kaun, Postdoctoral Fellow
Christopher Kliethermes, Postdoctoral Fellow
Eric Kong, Staff Research Associate
Amy Lasek, Senior Research Scientist
Rajani Maiya, Postdoctoral Fellow
Rolando Mancilla, Laboratory Assistant
Kimberly McClure, Postdoctoral Fellow
Galit Ophir, Postdoctoral Fellow
Dana Robertson, Graduate Student
Norma Velazquez Ulloa, Postdoctoral Fellow
Fred Wolf, Associate Investigator
Jeanette Wong, Administrative Assistant
Scholz H, Franz M, Heberlein U (2005) The hangover gene defines a stress pathway required for ethanol tolerance development. Nature 436:845-7.
Corl AB, Rodan AR, Heberlein U (2005) Insulin signaling in the nervous system regulates ethanol intoxication in Drosophila melanogaster . Nat Neurosci 8:18-19. PubMed Abstract
Berger KH, Heberlein U, Moore MS (2004) Rapid and chronic: two distinct forms of ethanol tolerance in Drosophila . Alcohol Clin Exp Res 10:1469-80.
Tsai LT, Bainton RJ, Blau J, Heberlein U (2004) Lmo mutants reveal a novel role for circadian pacemaker neurons in cocaine-induced behaviors. PLoS Biol 12:E408.
Cho W, Heberlein U, Wolf FW (2004) Habituation of an odorant-induced startle response in Drosophila . Genes Brain Behav 3:127-37.
Guarnieri DJ, Heberlein U (2003) Drosophila melanogaster , a genetic model system for alcohol research. Int Rev Neurobiol 54:199-228.
Rothenfluh A, Heberlein U. Drugs, flies, and videotape: the effects of ethanol and cocaine on Drosophila locomotion (2003) Curr Opin Neurobiol 6:639-45.
Wolf FW, Heberlein U (2003) Invertebrate models of drug abuse. J Neurobiol 54:161-78. Review.
Rodan AR, Kiger JA Jr, Heberlein U (2002) Functional dissection of neuroanatomical loci regulating ethanol sensitivity in Drosophila . J Neurosci 22:9490-501
Bainton, R. J., Tsai, L. T.-Y., Singh, C. M., Moore, M. S., Neckameyer, W. S., and Heberlein, U. (2000) Dopamine modulates acute responses to cocaine, nicotine, and ethanol in Drosophila. Current Biology. 10: 187-194.
Singh, C. M. and Heberlein, U. (2000) Genetic control of acute ethanol-induced behavior in Drosophila. Alcoholism: Clin. Exp. Res. In press.
Chanut, F., and Heberlein, U. (1997) Role of decapentaplegic in initiation and progression of the morphogenetic furrow in the developing Drosophila retina. Development 124:559Ð567.
Heberlein, U., Borod, E. R., and Chanut, F. A. (1998) Dorsoventral patterning in the Drosophila retina by wingless. Development 125:567Ð577.Moore, M. S., Dezazzo, J., Luk, A. Y., Tully, T., Singh, C. M., and Heberlein, U. (1998) Ethanol intoxication in Drosophila: Genetic and pharmacological evidence for regulation by the cAMP pathway. Cell 93: 997-1007.
Ulrike Heberlein, Ph.D.
1550 4th Street
Room RH 448F
Mission Bay Campus
1550 4th Street
San Francisco,CA 94158-2324
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