JPET Introducing ALZET?ew Model 2006 Pump

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gobbi, G.
Right arrow Articles by Blier, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gobbi, G.
Right arrow Articles by Blier, P.

Vol. 296, Issue 3, 987-995, March 2001

Modifications of the Serotonergic System in Mice Lacking Serotonin Transporters: An in Vivo Electrophysiological Study

Gabriella Gobbi, Dennis L. Murphy, Klaus-Peter Lesch and Pierre Blier

Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Canada (G.G.); Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland (D.L.M); Department of Psychiatry, University of Wurzburg, Würzburg, Germany (K.-P.L.); and Department of Psychiatry, University of Florida Brain Institute, Gainesville, Florida (P.B.)

The serotonin transporter (5-HTT) plays a key role in the regulation of serotonin (5-hydroxytryptamine, 5-HT) transmission in the pathophysiology and therapeutics of several psychiatric disorders. The mean spontaneous firing rate of midbrain dorsal raphe 5-HT neurons was recorded in chloral hydrate-anesthetized mice. The serotonin transporter (5-HTT), which plays a key role in the regulation of serotonin was significantly decreased in homozygous mice lacking the 5-HT transporter (5-HTT -/-) by 66% and in heterozygous (5-HTT +/-) mice by 36% compared with their normal littermates (5-HTT +/+). Systemic injection of the selective 5-HT1A receptor antagonist WAY 100635 enhanced 5-HT neuronal firing by 127% in 5-HT -/- mice, thus indicating an enhanced synaptic availability of 5-HT at inhibitory 5-HT1A receptors. Nevertheless, the cell body 5-HT1A autoreceptors were desensitized in both 5-HTT -/- and 5-HTT +/- mice. At the postsynaptic level, the recovery time (RT50) of the firing rate of hippocampus CA3 pyramidal neurons following iontophoretic applications of 5-HT was significantly prolonged only in 5-HTT -/- mice. The selective 5-HT reuptake inhibitor paroxetine significantly prolonged the RT50 in 5-HTT +/+ and 5-HTT +/- mice, without altering the maximal inhibitory effect of 5-HT. These neurons in 5-HTT -/- mice showed an attenuated response to the 5-HT1A agonist 8-hydroxy-2-diproplyaminotetralin, but not to 5-HT itself. These results establish that the lack of 5-HTT causes a prolonged recovery of firing activity following 5-HT applications. The genetic deletion of the 5-HTT plays a key role on 5-HT1A receptor adaptation: a desensitization at pre- and postsynaptic levels in 5-HTT -/- mice, but to a different extent, and only at the presynaptic level in the 5-HTT +/- group.

0022-3565/01/2963-0987$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Physiol.Home page
A. Li and E. Nattie
Serotonin transporter knockout mice have a reduced ventilatory response to hypercapnia (predominantly in males) but not to hypoxia
J. Physiol., May 1, 2008; 586(9): 2321 - 2329.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
L. N. Cornelisse, J. E. Van der Harst, J. C. Lodder, P.J.J. Baarendse, A. J. Timmerman, H. D. Mansvelder, B. M. Spruijt, and A. B. Brussaard
Reduced 5-HT1A- and GABAB Receptor Function in Dorsal Raphe Neurons Upon Chronic Fluoxetine Treatment of Socially Stressed Rats
J Neurophysiol, July 1, 2007; 98(1): 196 - 204.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
A. Neumeister, X.-Z. Hu, D. A. Luckenbaugh, M. Schwarz, A. C. Nugent, O. Bonne, P. Herscovitch, D. Goldman, W. C. Drevets, and D. S. Charney
Differential Effects of 5-HTTLPR Genotypes on the Behavioral and Neural Responses to Tryptophan Depletion in Patients With Major Depression and Controls.
Arch Gen Psychiatry, September 1, 2006; 63(9): 978 - 986.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. Alexandre, D. Popa, V. Fabre, S. Bouali, P. Venault, K.-P. Lesch, M. Hamon, and J. Adrien
Early life blockade of 5-hydroxytryptamine 1A receptors normalizes sleep and depression-like behavior in adult knock-out mice lacking the serotonin transporter.
J. Neurosci., May 17, 2006; 26(20): 5554 - 5564.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
P. R. Albert and S. Lemonde
5-HT1A Receptors, Gene Repression, and Depression: Guilt by Association
Neuroscientist, December 1, 2004; 10(6): 575 - 593.
[Abstract] [PDF]

Home page
 ScienceHome page
M. S. Ansorge, M. Zhou, A. Lira, R. Hen, and J. A. Gingrich
Early-Life Blockade of the 5-HT Transporter Alters Emotional Behavior in Adult Mice
Science, October 29, 2004; 306(5697): 879 - 881.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M.-T. Liu, S. Rayport, Y. Jiang, D. L. Murphy, and M. D. Gershon
Expression and function of 5-HT3 receptors in the enteric neurons of mice lacking the serotonin transporter
Am J Physiol Gastrointest Liver Physiol, December 1, 2002; 283(6): G1398 - G1411.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2001 by the American Society for Pharmacology and Experimental Therapeutics.