 |
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, August 15, 2001, 21(16):5871-5884
Mutations in the Caenorhabditis elegans Serotonin Reuptake Transporter MOD-5 Reveal Serotonin-Dependent and -Independent Activities of Fluoxetine
Rajesh Ranganathan, Elizabeth R. Sawin, Carol Trent, and H. Robert Horvitz Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
We isolated two mutants defective in the uptake of exogenous serotonin (5-HT) into the neurosecretory motor neurons of Caenorhabditis elegans. These mutants were hypersensitive to exogenous 5-HT and hyper-responsive in the experience-dependent enhanced slowing response to food modulated by 5-HT. The two allelic mutations defined the gene mod-5 (modulation of locomotion defective), which encodes the only serotonin reuptake transporter (SERT) in C. elegans. The selective serotonin reuptake inhibitor fluoxetine (Prozac) potentiated the enhanced slowing response, and this potentiation required mod-5 function, establishing a 5-HT- and SERT-dependent behavioral effect of fluoxetine in C. elegans. By contrast, other responses of C. elegans to fluoxetine were independent of MOD-5 SERT and 5-HT. Further analysis of the MOD-5-independent behavioral effects of fluoxetine could lead to the identification of novel targets of fluoxetine and could facilitate the development of more specific human pharmaceuticals.
Key words: C. elegans; SERT; fluoxetine; serotonin; reuptake; modulation of behavior; SSRI
Copyright © 2001 Society for Neuroscience 0270-6474/01/21165871-14$05.00/0
This article has been cited by other articles:
P. W. McDonald, S. L. Hardie, T. N. Jessen, L. Carvelli, D. S. Matthies, and R. D. Blakely
Vigorous Motor Activity in Caenorhabditis elegans Requires Efficient Clearance of Dopamine Mediated by Synaptic Localization of the Dopamine Transporter DAT-1
J. Neurosci., December 19, 2007; 27(51): 14216 - 14227.
[Abstract] [Full Text] [PDF]
Y. Wu, Z. Wu, P. Butko, Y. Christen, M. P. Lambert, W. L. Klein, C. D. Link, and Y. Luo
Amyloid-{beta}-Induced Pathological Behaviors Are Suppressed by Ginkgo biloba Extract EGb 761 and Ginkgolides in Transgenic Caenorhabditis elegans
J. Neurosci., December 13, 2006; 26(50): 13102 - 13113.
[Abstract] [Full Text] [PDF]
G. P. Mullen, E. A. Mathews, P. Saxena, S. D. Fields, J. R. McManus, G. Moulder, R. J. Barstead, M. W. Quick, and J. B. Rand
The Caenorhabditis elegans snf-11 Gene Encodes a Sodium-dependent GABA Transporter Required for Clearance of Synaptic GABA
Mol. Biol. Cell, July 1, 2006; 17(7): 3021 - 3030.
[Abstract] [Full Text] [PDF]
A. Mohri, E. Kodama, K. D. Kimura, M. Koike, T. Mizuno, and I. Mori
Genetic Control of Temperature Preference in the Nematode Caenorhabditis elegans
Genetics, March 1, 2005; 169(3): 1437 - 1450.
[Abstract] [Full Text] [PDF]
C. M. Dempsey, S. M. Mackenzie, A. Gargus, G. Blanco, and J. Y. Sze
Serotonin (5HT), Fluoxetine, Imipramine and Dopamine Target Distinct 5HT Receptor Signaling to Modulate Caenorhabditis elegans Egg-Laying Behavior
Genetics, March 1, 2005; 169(3): 1425 - 1436.
[Abstract] [Full Text] [PDF]
G. Jiang, L. Zhuang, S. Miyauchi, K. Miyake, Y.-J. Fei, and V. Ganapathy
A Na+/Cl--coupled GABA Transporter, GAT-1, from Caenorhabditis elegans: STRUCTURAL AND FUNCTIONAL FEATURES, SPECIFIC EXPRESSION IN GABA-ERGIC NEURONS, AND INVOLVEMENT IN MUSCLE FUNCTION
J. Biol. Chem., January 21, 2005; 280(3): 2065 - 2077.
[Abstract] [Full Text] [PDF]
M. Y. Chao, H. Komatsu, H. S. Fukuto, H. M. Dionne, and A. C. Hart
Feeding status and serotonin rapidly and reversibly modulate a Caenorhabditis elegans chemosensory circuit
PNAS, October 26, 2004; 101(43): 15512 - 15517.
[Abstract] [Full Text] [PDF]
M. B. Larsen, B. Elfving, and O. Wiborg
The Chicken Serotonin Transporter Discriminates between Serotonin-selective Reuptake Inhibitors: A SPECIES-SCANNING MUTAGENESIS STUDY
J. Biol. Chem., October 1, 2004; 279(40): 42147 - 42156.
[Abstract] [Full Text] [PDF]
G. Aspock, G. Ruvkun, and T. R. Burglin
The Caenorhabditis elegans ems class homeobox gene ceh-2 is required for M3 pharynx motoneuron function
Development, August 1, 2003; 130(15): 3369 - 3378.
[Abstract] [Full Text] [PDF]
A. Serafeim, M. J. Holder, G. Grafton, A. Chamba, M. T. Drayson, Q. T. Luong, C. M. Bunce, C. D. Gregory, N. M. Barnes, and J. Gordon
Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsy-like Burkitt lymphoma cells
Blood, April 15, 2003; 101(8): 3212 - 3219.
[Abstract] [Full Text] [PDF]
W. M. Nuttley, K. P. Atkinson-Leadbeater, and D. van der Kooy
Serotonin mediates food-odor associative learning in the nematode Caenorhabditiselegans
PNAS, September 17, 2002; 99(19): 12449 - 12454.
[Abstract] [Full Text] [PDF]
R. Nass, D. H. Hall, D. M. Miller III, and R. D. Blakely
Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans
PNAS, February 20, 2002; (2002) 42497999.
[Abstract] [Full Text] [PDF]
R. Nass, D. H. Hall, D. M. Miller III, and R. D. Blakely
Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans
PNAS, March 5, 2002; 99(5): 3264 - 3269.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|