5-HT2A and mGlu2 receptor binding levels are related to differences in impulsive behavior in the Roman Low- (RLA) and High- (RHA) avoidance rat strains

A B Klein; L Ultved; D Adamsen; Martin A Santini; A Tobeña; A Fernandez-Teruel; P Flores; M Moreno; D Cardona; Gitte Moos Knudsen; Susana Aznar; J D Mikkelsen

doi:10.1016/j.neuroscience.2013.12.063

5-HT_2A and mGlu2 receptor binding levels are related to differences in impulsive behavior in the Roman Low- (RLA) and High- (RHA) avoidance rat strains

A B Klein, L Ultved, D Adamsen, Martin A Santini, A Tobeña, A Fernandez-Teruel, P Flores, M Moreno, D Cardona, Gitte Moos Knudsen, Susana Aznar, J D Mikkelsen

Department of Clinical Medicine

40 Citations (Scopus)

Abstract

The Roman Low- and High-Avoidance rat strains (RLA-I vs RHA-I) have been bidirectionally selected and bred according to their performance in the two-way active avoidance response in the shuttle-box test. Numerous studies have reported a pronounced divergence in emotionality between the two rat strains including differences in novelty seeking, anxiety, stress coping, and susceptibility to addictive substances. However, the underlying molecular mechanisms behind these divergent phenotypes are not known. Here, we determined impulsivity using the 5-choice serial reaction time task and levels of serotonin transporter (SERT), 5-HT(2A) and 5-HT(1A) receptor binding using highly specific radioligands ((3)H-escitalopram, (3)H-MDL100907 and (3)H-WAY100635) and mGlu2/3 receptor binding ((3)H-LY341495) using receptor autoradiography in fronto-cortical sections from RLA-I (n=8) and RHA-I (n=8) male rats. In the more impulsive RHA-I rats, 5-HT(2A), 5-HT(1A) and SERT binding in the frontal cortex was significantly higher compared to RLA-I rats. In contrast, mGlu2/3 receptor binding was decreased by 40% in RHA-I rats compared to RLA-I rats. To differentiate between mGlu2 and mGlu3 receptor protein levels, these were further studied using western blotting, which showed non-detectable levels of mGlu2 receptor protein in RHA rats, while no differences were observed for mGlu3 receptor protein levels. Collectively, these data show general congenital differences in the serotonergic system and a pronounced difference in mGlu2 receptor protein levels. We suggest that the differences in the serotonergic system may mediate some of the phenotypic characteristics in this strain such as hyper-impulsivity and susceptibility to drug addiction.

Original language	English
Journal	Neuroscience
Volume	263
Pages (from-to)	36-45
Number of pages	10
ISSN	0306-4522
DOIs	https://doi.org/10.1016/j.neuroscience.2013.12.063
Publication status	Published - 28 Mar 2014

Keywords

Animals
Autoradiography
Frontal Lobe
Impulsive Behavior
Male
Rats
Rats, Inbred Strains
Receptor, Serotonin, 5-HT1A
Receptor, Serotonin, 5-HT2A
Receptors, Metabotropic Glutamate
Serotonin Plasma Membrane Transport Proteins

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.neuroscience.2013.12.063

Cite this

Klein, A. B., Ultved, L., Adamsen, D., Santini, M. A., Tobeña, A., Fernandez-Teruel, A., Flores, P., Moreno, M., Cardona, D., Knudsen, G. M., Aznar, S., & Mikkelsen, J. D. (2014). 5-HT_2A and mGlu2 receptor binding levels are related to differences in impulsive behavior in the Roman Low- (RLA) and High- (RHA) avoidance rat strains. Neuroscience, 263, 36-45. https://doi.org/10.1016/j.neuroscience.2013.12.063

Klein, AB, Ultved, L, Adamsen, D, Santini, MA, Tobeña, A, Fernandez-Teruel, A, Flores, P, Moreno, M, Cardona, D, Knudsen, GM, Aznar, S & Mikkelsen, JD 2014, '5-HT_2A and mGlu2 receptor binding levels are related to differences in impulsive behavior in the Roman Low- (RLA) and High- (RHA) avoidance rat strains', Neuroscience, vol. 263, pp. 36-45. https://doi.org/10.1016/j.neuroscience.2013.12.063

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abstract = "The Roman Low- and High-Avoidance rat strains (RLA-I vs RHA-I) have been bidirectionally selected and bred according to their performance in the two-way active avoidance response in the shuttle-box test. Numerous studies have reported a pronounced divergence in emotionality between the two rat strains including differences in novelty seeking, anxiety, stress coping, and susceptibility to addictive substances. However, the underlying molecular mechanisms behind these divergent phenotypes are not known. Here, we determined impulsivity using the 5-choice serial reaction time task and levels of serotonin transporter (SERT), 5-HT(2A) and 5-HT(1A) receptor binding using highly specific radioligands ((3)H-escitalopram, (3)H-MDL100907 and (3)H-WAY100635) and mGlu2/3 receptor binding ((3)H-LY341495) using receptor autoradiography in fronto-cortical sections from RLA-I (n=8) and RHA-I (n=8) male rats. In the more impulsive RHA-I rats, 5-HT(2A), 5-HT(1A) and SERT binding in the frontal cortex was significantly higher compared to RLA-I rats. In contrast, mGlu2/3 receptor binding was decreased by 40% in RHA-I rats compared to RLA-I rats. To differentiate between mGlu2 and mGlu3 receptor protein levels, these were further studied using western blotting, which showed non-detectable levels of mGlu2 receptor protein in RHA rats, while no differences were observed for mGlu3 receptor protein levels. Collectively, these data show general congenital differences in the serotonergic system and a pronounced difference in mGlu2 receptor protein levels. We suggest that the differences in the serotonergic system may mediate some of the phenotypic characteristics in this strain such as hyper-impulsivity and susceptibility to drug addiction.",

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T1 - 5-HT2A and mGlu2 receptor binding levels are related to differences in impulsive behavior in the Roman Low- (RLA) and High- (RHA) avoidance rat strains

AU - Klein, A B

AU - Ultved, L

AU - Adamsen, D

AU - Santini, Martin A

AU - Tobeña, A

AU - Fernandez-Teruel, A

AU - Flores, P

AU - Moreno, M

AU - Cardona, D

AU - Knudsen, Gitte Moos

AU - Aznar, Susana

AU - Mikkelsen, J D

PY - 2014/3/28

Y1 - 2014/3/28

N2 - The Roman Low- and High-Avoidance rat strains (RLA-I vs RHA-I) have been bidirectionally selected and bred according to their performance in the two-way active avoidance response in the shuttle-box test. Numerous studies have reported a pronounced divergence in emotionality between the two rat strains including differences in novelty seeking, anxiety, stress coping, and susceptibility to addictive substances. However, the underlying molecular mechanisms behind these divergent phenotypes are not known. Here, we determined impulsivity using the 5-choice serial reaction time task and levels of serotonin transporter (SERT), 5-HT(2A) and 5-HT(1A) receptor binding using highly specific radioligands ((3)H-escitalopram, (3)H-MDL100907 and (3)H-WAY100635) and mGlu2/3 receptor binding ((3)H-LY341495) using receptor autoradiography in fronto-cortical sections from RLA-I (n=8) and RHA-I (n=8) male rats. In the more impulsive RHA-I rats, 5-HT(2A), 5-HT(1A) and SERT binding in the frontal cortex was significantly higher compared to RLA-I rats. In contrast, mGlu2/3 receptor binding was decreased by 40% in RHA-I rats compared to RLA-I rats. To differentiate between mGlu2 and mGlu3 receptor protein levels, these were further studied using western blotting, which showed non-detectable levels of mGlu2 receptor protein in RHA rats, while no differences were observed for mGlu3 receptor protein levels. Collectively, these data show general congenital differences in the serotonergic system and a pronounced difference in mGlu2 receptor protein levels. We suggest that the differences in the serotonergic system may mediate some of the phenotypic characteristics in this strain such as hyper-impulsivity and susceptibility to drug addiction.

AB - The Roman Low- and High-Avoidance rat strains (RLA-I vs RHA-I) have been bidirectionally selected and bred according to their performance in the two-way active avoidance response in the shuttle-box test. Numerous studies have reported a pronounced divergence in emotionality between the two rat strains including differences in novelty seeking, anxiety, stress coping, and susceptibility to addictive substances. However, the underlying molecular mechanisms behind these divergent phenotypes are not known. Here, we determined impulsivity using the 5-choice serial reaction time task and levels of serotonin transporter (SERT), 5-HT(2A) and 5-HT(1A) receptor binding using highly specific radioligands ((3)H-escitalopram, (3)H-MDL100907 and (3)H-WAY100635) and mGlu2/3 receptor binding ((3)H-LY341495) using receptor autoradiography in fronto-cortical sections from RLA-I (n=8) and RHA-I (n=8) male rats. In the more impulsive RHA-I rats, 5-HT(2A), 5-HT(1A) and SERT binding in the frontal cortex was significantly higher compared to RLA-I rats. In contrast, mGlu2/3 receptor binding was decreased by 40% in RHA-I rats compared to RLA-I rats. To differentiate between mGlu2 and mGlu3 receptor protein levels, these were further studied using western blotting, which showed non-detectable levels of mGlu2 receptor protein in RHA rats, while no differences were observed for mGlu3 receptor protein levels. Collectively, these data show general congenital differences in the serotonergic system and a pronounced difference in mGlu2 receptor protein levels. We suggest that the differences in the serotonergic system may mediate some of the phenotypic characteristics in this strain such as hyper-impulsivity and susceptibility to drug addiction.

KW - Animals

KW - Autoradiography

KW - Frontal Lobe

KW - Impulsive Behavior

KW - Male

KW - Rats

KW - Rats, Inbred Strains

KW - Receptor, Serotonin, 5-HT1A

KW - Receptor, Serotonin, 5-HT2A

KW - Receptors, Metabotropic Glutamate

KW - Serotonin Plasma Membrane Transport Proteins

U2 - 10.1016/j.neuroscience.2013.12.063

DO - 10.1016/j.neuroscience.2013.12.063

M3 - Journal article

C2 - 24412375

SN - 0306-4522

VL - 263

SP - 36

EP - 45

JO - Neuroscience

JF - Neuroscience

ER -