Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor

Régis Grailhe; Christian Waeber; Stephanie C. Dulawa; Jean P. Hornung; Xiaoxi Zhuang; Dani Brunner; Mark A. Geyer; René Hen

doi:10.1016/S0896-6273(00)80712-6

Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor

Régis Grailhe
, Christian Waeber
, Stephanie C. Dulawa
, Jean P. Hornung
, Xiaoxi Zhuang
, Dani Brunner
, Mark A. Geyer
, René Hen

Research output: Contribution to journal › Article › peer-review

Abstract

In order to determine the distribution and function of the 5-HT(5A) serotonin receptor subtype, we generated knockout mice lacking the 5-HT(5A) gene. Comparative autoradiography studies of brains of wild-type (wt) and 5- HT(5A) knockout (5A-KO) mice revealed the existence of binding sites with high affinity for [¹²⁵I]LSD that correspond to 5-HT(5A) receptors and that are concentrated in the olfactory bulb, neocortex, and medial habenula. When exposed to novel environments, the 5A-KO mice displayed increased exploratory activity but no change in anxiety-related behaviors. In addition, the stimulatory effect of LSD on exploratory activity was attenuated in 5A-KO mice. These results suggest that 5-HT(5A) receptors modulate the activity of neural circuits involved specifically in exploratory behavior and suggest that some of the psychotropic effects of LSD may be mediated by 5-HT(5A) receptors.

Original language	English
Pages (from-to)	581-591
Number of pages	11
Journal	Neuron
Volume	22
Issue number	3
DOIs	https://doi.org/10.1016/S0896-6273(00)80712-6
Publication status	Published - Mar 1999
Externally published	Yes

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title = "Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor",

abstract = "In order to determine the distribution and function of the 5-HT(5A) serotonin receptor subtype, we generated knockout mice lacking the 5-HT(5A) gene. Comparative autoradiography studies of brains of wild-type (wt) and 5- HT(5A) knockout (5A-KO) mice revealed the existence of binding sites with high affinity for [125I]LSD that correspond to 5-HT(5A) receptors and that are concentrated in the olfactory bulb, neocortex, and medial habenula. When exposed to novel environments, the 5A-KO mice displayed increased exploratory activity but no change in anxiety-related behaviors. In addition, the stimulatory effect of LSD on exploratory activity was attenuated in 5A-KO mice. These results suggest that 5-HT(5A) receptors modulate the activity of neural circuits involved specifically in exploratory behavior and suggest that some of the psychotropic effects of LSD may be mediated by 5-HT(5A) receptors.",

author = "R{\'e}gis Grailhe and Christian Waeber and Dulawa, \{Stephanie C.\} and Hornung, \{Jean P.\} and Xiaoxi Zhuang and Dani Brunner and Geyer, \{Mark A.\} and Ren{\'e} Hen",

year = "1999",

month = mar,

doi = "10.1016/S0896-6273(00)80712-6",

language = "English",

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T1 - Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor

AU - Grailhe, Régis

AU - Waeber, Christian

AU - Dulawa, Stephanie C.

AU - Hornung, Jean P.

AU - Zhuang, Xiaoxi

AU - Brunner, Dani

AU - Geyer, Mark A.

AU - Hen, René

PY - 1999/3

Y1 - 1999/3

N2 - In order to determine the distribution and function of the 5-HT(5A) serotonin receptor subtype, we generated knockout mice lacking the 5-HT(5A) gene. Comparative autoradiography studies of brains of wild-type (wt) and 5- HT(5A) knockout (5A-KO) mice revealed the existence of binding sites with high affinity for [125I]LSD that correspond to 5-HT(5A) receptors and that are concentrated in the olfactory bulb, neocortex, and medial habenula. When exposed to novel environments, the 5A-KO mice displayed increased exploratory activity but no change in anxiety-related behaviors. In addition, the stimulatory effect of LSD on exploratory activity was attenuated in 5A-KO mice. These results suggest that 5-HT(5A) receptors modulate the activity of neural circuits involved specifically in exploratory behavior and suggest that some of the psychotropic effects of LSD may be mediated by 5-HT(5A) receptors.

AB - In order to determine the distribution and function of the 5-HT(5A) serotonin receptor subtype, we generated knockout mice lacking the 5-HT(5A) gene. Comparative autoradiography studies of brains of wild-type (wt) and 5- HT(5A) knockout (5A-KO) mice revealed the existence of binding sites with high affinity for [125I]LSD that correspond to 5-HT(5A) receptors and that are concentrated in the olfactory bulb, neocortex, and medial habenula. When exposed to novel environments, the 5A-KO mice displayed increased exploratory activity but no change in anxiety-related behaviors. In addition, the stimulatory effect of LSD on exploratory activity was attenuated in 5A-KO mice. These results suggest that 5-HT(5A) receptors modulate the activity of neural circuits involved specifically in exploratory behavior and suggest that some of the psychotropic effects of LSD may be mediated by 5-HT(5A) receptors.

UR - https://www.scopus.com/pages/publications/0033103167

U2 - 10.1016/S0896-6273(00)80712-6

DO - 10.1016/S0896-6273(00)80712-6

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AN - SCOPUS:0033103167

SN - 0896-6273

VL - 22

SP - 581

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JO - Neuron

JF - Neuron

IS - 3

ER -

Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor

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