DOI: 10.1073/pnas.95.24.14476. Serotonin receptor 1A knockout: An animal model of anxiety-related disorder [Penn]

Serotonin receptor 1A knockout: An animal model of anxiety-related disorder

10.1073/pnas.95.24.14476

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

To investigate the contribution of individual serotonin (5-hydroxytryptamine; 5-HT) receptors to mood control, we have used homologous recombination to generate mice lacking specific serotonergic receptor subtypes. In the present report, we demonstrate that mice without 5-HT1A receptors display decreased exploratory activity and increased fear of aversive environments (open or elevated spaces). 5-HT1A knockout mice also exhibited a decreased immobility in the forced swim test, an effect commonly associated with antidepressant treatment. Although 5-HT1A receptors are involved in controlling the activity of serotonergic neurons, 5-HT1A knockout mice had normal levels of 5-HT and 5-hydroxyindoleacetic acid, possibly because of an up-regulation of 5-HT1B autoreceptors. Heterozygote 5-HT1A mutants expressed approximately one-half of wild-type receptor density and displayed intermediate phenotypes in most behavioral tests. These results demonstrate that 5-HT1A receptors are involved in the modulation of exploratory and fear-related behaviors and suggest that reductions in 5-HT1A receptor density due to genetic defects or environmental stressors might result in heightened anxiety.

Bibliography

Ramboz, S., Oosting, R., Amara, D. A., Kung, H. F., Blier, P., Mendelsohn, M., Mann, J. J., Brunner, D., & Hen, R. (1998). Serotonin receptor 1A knockout: An animal model of anxiety-related disorder. Proceedings of the National Academy of Sciences, 95(24), 14476â14481.

Authors 9

Sylvie Ramboz (first)
Ronald Oosting (additional)
Djamel Aït Amara (additional)
Hank F. Kung (additional)
Pierre Blier (additional)
Monica Mendelsohn (additional)
J. John Mann (additional)
Dani Brunner (additional)
René Hen (additional)

References 34 Referenced 661

M Hamon Serotoninergic Neurons and 5-HT Receptors in the CNS, eds H G Baumgarten, M Göthert (Springer, Berlin), pp. 238–268 (1997). / Serotoninergic Neurons and 5-HT Receptors in the CNS by Hamon M (1997)
10.1111/j.1600-0773.1991.tb01289.x
10.1001/archpsyc.1994.03950030084009
P M Whitaker-Azmitia Pharmacol Rev 43, 553–561 (1991). / Pharmacol Rev by Whitaker-Azmitia P M (1991)
10.1073/pnas.92.16.7182
10.1038/329075a0
10.1038/305140a0
M P Kung, D Frederick, M Mu, Z P Zhuang, H F Kung J Pharmacol Exp Ther 272, 429–437 (1995). / J Pharmacol Exp Ther by Kung M P (1995)
10.1002/syn.890050206
10.1001/archpsyc.1986.01800060088011
10.1016/S0021-9258(19)52451-6
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10.1016/0006-8993(84)90664-4
10.1016/0197-0186(91)90063-J
10.1007/BF02245588
10.1016/0091-3057(92)90169-G
10.1126/science.8091214
10.1016/0006-8993(95)00523-S
C A Fornal, C W Metzler, R A Gallegos, S C Veasey, A C McCreary, B L Jacobs J Pharmacol Exp Ther 278, 752–762 (1996). / J Pharmacol Exp Ther by Fornal C A (1996)
10.1016/0166-4328(96)00118-0
10.1097/00001756-199512290-00084
10.1523/JNEUROSCI.16-15-04810.1996
S E File Experimental Approaches to Anxiety and Depression, eds J M Elliott, D J Heal, C A Marsden (Wiley, New York), pp. 26–44 (1992). / Experimental Approaches to Anxiety and Depression by File S E (1992)
10.1038/266730a0
10.1016/0165-6147(94)90315-8
10.1159/000119058
D Brunner, R Hen The Neurobiology of Suicide: From the Bench to the Clinic, eds D M Stoff, J J Mann (New York Academy of Sciences, New York), pp. 81–105 (1997). / The Neurobiology of Suicide: From the Bench to the Clinic by Brunner D (1997)
P Tyrer Experimental Approaches to Anxiety and Depression, eds J M Elliott, D J Heal, C A Marsden (Wiley, New York), pp. 9–25 (1992). / Experimental Approaches to Anxiety and Depression by Tyrer P (1992)
10.1016/0091-3057(95)02135-3
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10.1016/S0006-3223(98)00040-7

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:35 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:56 p.m.)
Indexed	1 week, 3 days ago (Aug. 23, 2025, 12:58 a.m.)
Issued	26 years, 9 months ago (Nov. 24, 1998)
Published	26 years, 9 months ago (Nov. 24, 1998)
Published Online	26 years, 9 months ago (Nov. 24, 1998)
Published Print	26 years, 9 months ago (Nov. 24, 1998)

Funders 0

None

BibTeX

@article{Ramboz_1998, title={Serotonin receptor 1A knockout: An animal model of anxiety-related disorder}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.24.14476}, DOI={10.1073/pnas.95.24.14476}, number={24}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Ramboz, Sylvie and Oosting, Ronald and Amara, Djamel Aït and Kung, Hank F. and Blier, Pierre and Mendelsohn, Monica and Mann, J. John and Brunner, Dani and Hen, René}, year={1998}, month=nov, pages={14476–14481} }

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