The brain 5-HT4 receptor binding is down-regulated in the Flinders Sensitive Line depression model and in response to paroxetine administration

Cecilie L Licht; Anders B Marcussen; Gregers Wegener; David H Overstreet; Susana Aznar; Gitte M Knudsen

doi:10.1111/j.1471-4159.2009.06050.x

The brain 5-HT4 receptor binding is down-regulated in the Flinders Sensitive Line depression model and in response to paroxetine administration

Cecilie L Licht, Anders B Marcussen, Gregers Wegener, David H Overstreet, Susana Aznar, Gitte M Knudsen

79 Citations (Scopus)

Abstract

The 5-hydroxytryptamine (5-HT(4)) receptor may be implicated in depression and is a new potential target for antidepressant treatment. We have investigated the brain 5-HT(4) receptor [(3)H]SB207145 binding in the Flinders Sensitive Line rat depression model by quantitative receptor autoradiography, and related this to 5-HT transporter (S)-[N-methyl-(3)H]citalopram binding. We also determined the regulation of 5-HT(4) receptor binding by 1, 14, and 21 days of paroxetine administration and subchronic 5-HT depletion, and compared this with changes in 5-HT(2A) receptor [(3)H]MDL100907 binding. In the Flinders Sensitive Line, the 5-HT(4) receptor and 5-HT transporter binding were decreased in the dorsal and ventral hippocampus, and the changes in binding were directly correlated within the dorsal hippocampus. Chronic but not acute paroxetine administration caused a 16-47% down-regulation of 5-HT(4) receptor binding in all regions evaluated including the basal ganglia and hippocampus, while 5-HT depletion increased the 5-HT(4) receptor binding in the dorsal hippocampus, hypothalamus, and lateral globus pallidus. In comparison, the 5-HT(2A) receptor binding was decreased in the frontal and cingulate cortices after chronic paroxetine administration, and markedly reduced in several regions after 5-HT depletion. Thus, the 5-HT(4) receptor binding was decreased in the Flinders Sensitive Line depression model and in response to chronic paroxetine administration.

Original language	English
Journal	Journal of Neurochemistry
Volume	109
Issue number	5
Pages (from-to)	1363-74
Number of pages	12
ISSN	0022-3042
DOIs	https://doi.org/10.1111/j.1471-4159.2009.06050.x
Publication status	Published - Jun 2009

Keywords

Animals
Antidepressive Agents, Second-Generation
Autoradiography
Brain
Citalopram
Depression
Disease Models, Animal
Fenclonine
Fenfluramine
Fluorobenzenes
Freezing Reaction, Cataleptic
Male
Paroxetine
Piperidines
Protein Binding
Rats
Rats, Inbred Strains
Rats, Sprague-Dawley
Receptors, Serotonin, 5-HT4
Serotonin
Serotonin Antagonists
Serotonin Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors
Swimming
Time Factors
Tritium

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10.1111/j.1471-4159.2009.06050.x

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@article{ec00073f5f9f42f49d93344b4c2eef8d,

title = "The brain 5-HT4 receptor binding is down-regulated in the Flinders Sensitive Line depression model and in response to paroxetine administration",

abstract = "The 5-hydroxytryptamine (5-HT(4)) receptor may be implicated in depression and is a new potential target for antidepressant treatment. We have investigated the brain 5-HT(4) receptor [(3)H]SB207145 binding in the Flinders Sensitive Line rat depression model by quantitative receptor autoradiography, and related this to 5-HT transporter (S)-[N-methyl-(3)H]citalopram binding. We also determined the regulation of 5-HT(4) receptor binding by 1, 14, and 21 days of paroxetine administration and subchronic 5-HT depletion, and compared this with changes in 5-HT(2A) receptor [(3)H]MDL100907 binding. In the Flinders Sensitive Line, the 5-HT(4) receptor and 5-HT transporter binding were decreased in the dorsal and ventral hippocampus, and the changes in binding were directly correlated within the dorsal hippocampus. Chronic but not acute paroxetine administration caused a 16-47% down-regulation of 5-HT(4) receptor binding in all regions evaluated including the basal ganglia and hippocampus, while 5-HT depletion increased the 5-HT(4) receptor binding in the dorsal hippocampus, hypothalamus, and lateral globus pallidus. In comparison, the 5-HT(2A) receptor binding was decreased in the frontal and cingulate cortices after chronic paroxetine administration, and markedly reduced in several regions after 5-HT depletion. Thus, the 5-HT(4) receptor binding was decreased in the Flinders Sensitive Line depression model and in response to chronic paroxetine administration.",

keywords = "Animals, Antidepressive Agents, Second-Generation, Autoradiography, Brain, Citalopram, Depression, Disease Models, Animal, Fenclonine, Fenfluramine, Fluorobenzenes, Freezing Reaction, Cataleptic, Male, Paroxetine, Piperidines, Protein Binding, Rats, Rats, Inbred Strains, Rats, Sprague-Dawley, Receptors, Serotonin, 5-HT4, Serotonin, Serotonin Antagonists, Serotonin Plasma Membrane Transport Proteins, Serotonin Uptake Inhibitors, Swimming, Time Factors, Tritium",

author = "Licht, {Cecilie L} and Marcussen, {Anders B} and Gregers Wegener and Overstreet, {David H} and Susana Aznar and Knudsen, {Gitte M}",

year = "2009",

month = jun,

doi = "10.1111/j.1471-4159.2009.06050.x",

language = "English",

volume = "109",

pages = "1363--74",

journal = "Journal of Neurochemistry",

issn = "0022-3042",

publisher = "Wiley-Blackwell Publishing Ltd",

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TY - JOUR

T1 - The brain 5-HT4 receptor binding is down-regulated in the Flinders Sensitive Line depression model and in response to paroxetine administration

AU - Licht, Cecilie L

AU - Marcussen, Anders B

AU - Wegener, Gregers

AU - Overstreet, David H

AU - Aznar, Susana

AU - Knudsen, Gitte M

PY - 2009/6

Y1 - 2009/6

N2 - The 5-hydroxytryptamine (5-HT(4)) receptor may be implicated in depression and is a new potential target for antidepressant treatment. We have investigated the brain 5-HT(4) receptor [(3)H]SB207145 binding in the Flinders Sensitive Line rat depression model by quantitative receptor autoradiography, and related this to 5-HT transporter (S)-[N-methyl-(3)H]citalopram binding. We also determined the regulation of 5-HT(4) receptor binding by 1, 14, and 21 days of paroxetine administration and subchronic 5-HT depletion, and compared this with changes in 5-HT(2A) receptor [(3)H]MDL100907 binding. In the Flinders Sensitive Line, the 5-HT(4) receptor and 5-HT transporter binding were decreased in the dorsal and ventral hippocampus, and the changes in binding were directly correlated within the dorsal hippocampus. Chronic but not acute paroxetine administration caused a 16-47% down-regulation of 5-HT(4) receptor binding in all regions evaluated including the basal ganglia and hippocampus, while 5-HT depletion increased the 5-HT(4) receptor binding in the dorsal hippocampus, hypothalamus, and lateral globus pallidus. In comparison, the 5-HT(2A) receptor binding was decreased in the frontal and cingulate cortices after chronic paroxetine administration, and markedly reduced in several regions after 5-HT depletion. Thus, the 5-HT(4) receptor binding was decreased in the Flinders Sensitive Line depression model and in response to chronic paroxetine administration.

AB - The 5-hydroxytryptamine (5-HT(4)) receptor may be implicated in depression and is a new potential target for antidepressant treatment. We have investigated the brain 5-HT(4) receptor [(3)H]SB207145 binding in the Flinders Sensitive Line rat depression model by quantitative receptor autoradiography, and related this to 5-HT transporter (S)-[N-methyl-(3)H]citalopram binding. We also determined the regulation of 5-HT(4) receptor binding by 1, 14, and 21 days of paroxetine administration and subchronic 5-HT depletion, and compared this with changes in 5-HT(2A) receptor [(3)H]MDL100907 binding. In the Flinders Sensitive Line, the 5-HT(4) receptor and 5-HT transporter binding were decreased in the dorsal and ventral hippocampus, and the changes in binding were directly correlated within the dorsal hippocampus. Chronic but not acute paroxetine administration caused a 16-47% down-regulation of 5-HT(4) receptor binding in all regions evaluated including the basal ganglia and hippocampus, while 5-HT depletion increased the 5-HT(4) receptor binding in the dorsal hippocampus, hypothalamus, and lateral globus pallidus. In comparison, the 5-HT(2A) receptor binding was decreased in the frontal and cingulate cortices after chronic paroxetine administration, and markedly reduced in several regions after 5-HT depletion. Thus, the 5-HT(4) receptor binding was decreased in the Flinders Sensitive Line depression model and in response to chronic paroxetine administration.

KW - Animals

KW - Antidepressive Agents, Second-Generation

KW - Autoradiography

KW - Brain

KW - Citalopram

KW - Depression

KW - Disease Models, Animal

KW - Fenclonine

KW - Fenfluramine

KW - Fluorobenzenes

KW - Freezing Reaction, Cataleptic

KW - Male

KW - Paroxetine

KW - Piperidines

KW - Protein Binding

KW - Rats

KW - Rats, Inbred Strains

KW - Rats, Sprague-Dawley

KW - Receptors, Serotonin, 5-HT4

KW - Serotonin

KW - Serotonin Antagonists

KW - Serotonin Plasma Membrane Transport Proteins

KW - Serotonin Uptake Inhibitors

KW - Swimming

KW - Time Factors

KW - Tritium

U2 - 10.1111/j.1471-4159.2009.06050.x

DO - 10.1111/j.1471-4159.2009.06050.x

M3 - Journal article

C2 - 19476548

SN - 0022-3042

VL - 109

SP - 1363

EP - 1374

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

IS - 5

ER -

The brain 5-HT4 receptor binding is down-regulated in the Flinders Sensitive Line depression model and in response to paroxetine administration

Abstract

Keywords

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