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
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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. / Klein, A B; Ultved, L; Adamsen, D; Santini, Martin A; Tobeña, A; Fernandez-Teruel, A; Flores, P; Moreno, M; Cardona, D; Knudsen, Gitte Moos; Aznar, Susana; Mikkelsen, J D.
In: Neuroscience, Vol. 263, 28.03.2014, p. 36-45.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
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
N1 - Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
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
VL - 263
SP - 36
EP - 45
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
ER -
ID: 138183837