Acute tryptophan depletion dose dependently impairs object memory in serotonin transporter knockout rats

J. D. A. Olivier; L. A. W. Jans; G. A. H. Korte-Bouws; S. M. Korte; P. M. T. Deen; A. R. Cools; B. A. Ellenbroek; A. Blokland

doi:10.1007/s00213-008-1201-0

Acute tryptophan depletion dose dependently impairs object memory in serotonin transporter knockout rats

J. D. A. Olivier^*, L. A. W. Jans, G. A. H. Korte-Bouws, S. M. Korte, P. M. T. Deen, A. R. Cools, B. A. Ellenbroek, A. Blokland

^*Corresponding author for this work

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

Abstract

Rationale Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats.

Objectives As individual differences exist in central serotonin neurotransmission, the impact of ATD may vary accordingly. In this experiment, we investigated the hypothesis that male serotonin transporter knockout (SERT(-/-)), rats marked by a lower SERT function, are more vulnerable to the effects of ATD in an object recognition task than male wildtype (SERT(+/+)) and heterozygous (SERT(+/-)) rats.

Materials and methods Twelve male SERT(+/+), SERT(+-), and SERT(-/-) rats were treated with standard dose and low-dose ATD using a gelatine-based protein-carbohydrate mixture lacking tryptophan. In the control treatment, L-tryptophan was added to the mixture. Four hours after treatment, the rats were subjected to the object recognition task. In addition, the effects of ATD on plasma amino acid concentrations were measured, and concentrations of 5-HT and 5-HIAA were measured in the frontal cortex and hippocampus of these rats.

Results Plasma TRP levels and central 5-HT and 5-HIAA levels were decreased in all genotypes after ATD, but effects were stronger in SERT(-/-) rats. The standard dose of ATD impaired object recognition in all genotypes. SERT(-/-) and SERT(+/-) rats were more vulnerable to low dose of ATD in the object recognition task compared to SERT(+/+) rats.

Conclusions These results indicate a greater sensitivity to ATD in SERT(-/-) and SERT(+/-) rats, which may be related to stronger central depletion effects in these rats.

Original language	English
Pages (from-to)	243-254
Number of pages	12
Journal	Psychopharmacology
Volume	200
Issue number	2
DOIs	https://doi.org/10.1007/s00213-008-1201-0
Publication status	Published - Oct 2008

Keywords

acute tryptophan depletion
knockout
serotonin
serotonin transporter
object recognition
5-HIAA
hippocampus
frontal cortex
GELATIN-BASED MIXTURE
AMINO-ACID MIXTURES
BRAIN TRYPTOPHAN
COGNITIVE FUNCTIONS
SERUM TRYPTOPHAN
RECOGNITION
MOOD
POLYMORPHISM
DEPRESSION
VOLUNTEERS

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10.1007/s00213-008-1201-0

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@article{a3c57a67e3d7463c9a0225b48f87428e,

title = "Acute tryptophan depletion dose dependently impairs object memory in serotonin transporter knockout rats",

abstract = "Rationale Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats.Objectives As individual differences exist in central serotonin neurotransmission, the impact of ATD may vary accordingly. In this experiment, we investigated the hypothesis that male serotonin transporter knockout (SERT(-/-)), rats marked by a lower SERT function, are more vulnerable to the effects of ATD in an object recognition task than male wildtype (SERT(+/+)) and heterozygous (SERT(+/-)) rats.Materials and methods Twelve male SERT(+/+), SERT(+-), and SERT(-/-) rats were treated with standard dose and low-dose ATD using a gelatine-based protein-carbohydrate mixture lacking tryptophan. In the control treatment, L-tryptophan was added to the mixture. Four hours after treatment, the rats were subjected to the object recognition task. In addition, the effects of ATD on plasma amino acid concentrations were measured, and concentrations of 5-HT and 5-HIAA were measured in the frontal cortex and hippocampus of these rats.Results Plasma TRP levels and central 5-HT and 5-HIAA levels were decreased in all genotypes after ATD, but effects were stronger in SERT(-/-) rats. The standard dose of ATD impaired object recognition in all genotypes. SERT(-/-) and SERT(+/-) rats were more vulnerable to low dose of ATD in the object recognition task compared to SERT(+/+) rats.Conclusions These results indicate a greater sensitivity to ATD in SERT(-/-) and SERT(+/-) rats, which may be related to stronger central depletion effects in these rats.",

keywords = "acute tryptophan depletion, knockout, serotonin, serotonin transporter, object recognition, 5-HIAA, hippocampus, frontal cortex, GELATIN-BASED MIXTURE, AMINO-ACID MIXTURES, BRAIN TRYPTOPHAN, COGNITIVE FUNCTIONS, SERUM TRYPTOPHAN, RECOGNITION, MOOD, POLYMORPHISM, DEPRESSION, VOLUNTEERS",

author = "Olivier, {J. D. A.} and Jans, {L. A. W.} and Korte-Bouws, {G. A. H.} and Korte, {S. M.} and Deen, {P. M. T.} and Cools, {A. R.} and Ellenbroek, {B. A.} and A. Blokland",

year = "2008",

month = oct,

doi = "10.1007/s00213-008-1201-0",

language = "English",

volume = "200",

pages = "243--254",

journal = "Psychopharmacology",

issn = "0033-3158",

publisher = "Springer",

number = "2",

}

TY - JOUR

T1 - Acute tryptophan depletion dose dependently impairs object memory in serotonin transporter knockout rats

AU - Olivier, J. D. A.

AU - Jans, L. A. W.

AU - Korte-Bouws, G. A. H.

AU - Korte, S. M.

AU - Deen, P. M. T.

AU - Cools, A. R.

AU - Ellenbroek, B. A.

AU - Blokland, A.

PY - 2008/10

Y1 - 2008/10

N2 - Rationale Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats.Objectives As individual differences exist in central serotonin neurotransmission, the impact of ATD may vary accordingly. In this experiment, we investigated the hypothesis that male serotonin transporter knockout (SERT(-/-)), rats marked by a lower SERT function, are more vulnerable to the effects of ATD in an object recognition task than male wildtype (SERT(+/+)) and heterozygous (SERT(+/-)) rats.Materials and methods Twelve male SERT(+/+), SERT(+-), and SERT(-/-) rats were treated with standard dose and low-dose ATD using a gelatine-based protein-carbohydrate mixture lacking tryptophan. In the control treatment, L-tryptophan was added to the mixture. Four hours after treatment, the rats were subjected to the object recognition task. In addition, the effects of ATD on plasma amino acid concentrations were measured, and concentrations of 5-HT and 5-HIAA were measured in the frontal cortex and hippocampus of these rats.Results Plasma TRP levels and central 5-HT and 5-HIAA levels were decreased in all genotypes after ATD, but effects were stronger in SERT(-/-) rats. The standard dose of ATD impaired object recognition in all genotypes. SERT(-/-) and SERT(+/-) rats were more vulnerable to low dose of ATD in the object recognition task compared to SERT(+/+) rats.Conclusions These results indicate a greater sensitivity to ATD in SERT(-/-) and SERT(+/-) rats, which may be related to stronger central depletion effects in these rats.

AB - Rationale Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats.Objectives As individual differences exist in central serotonin neurotransmission, the impact of ATD may vary accordingly. In this experiment, we investigated the hypothesis that male serotonin transporter knockout (SERT(-/-)), rats marked by a lower SERT function, are more vulnerable to the effects of ATD in an object recognition task than male wildtype (SERT(+/+)) and heterozygous (SERT(+/-)) rats.Materials and methods Twelve male SERT(+/+), SERT(+-), and SERT(-/-) rats were treated with standard dose and low-dose ATD using a gelatine-based protein-carbohydrate mixture lacking tryptophan. In the control treatment, L-tryptophan was added to the mixture. Four hours after treatment, the rats were subjected to the object recognition task. In addition, the effects of ATD on plasma amino acid concentrations were measured, and concentrations of 5-HT and 5-HIAA were measured in the frontal cortex and hippocampus of these rats.Results Plasma TRP levels and central 5-HT and 5-HIAA levels were decreased in all genotypes after ATD, but effects were stronger in SERT(-/-) rats. The standard dose of ATD impaired object recognition in all genotypes. SERT(-/-) and SERT(+/-) rats were more vulnerable to low dose of ATD in the object recognition task compared to SERT(+/+) rats.Conclusions These results indicate a greater sensitivity to ATD in SERT(-/-) and SERT(+/-) rats, which may be related to stronger central depletion effects in these rats.

KW - acute tryptophan depletion

KW - knockout

KW - serotonin

KW - serotonin transporter

KW - object recognition

KW - 5-HIAA

KW - hippocampus

KW - frontal cortex

KW - GELATIN-BASED MIXTURE

KW - AMINO-ACID MIXTURES

KW - BRAIN TRYPTOPHAN

KW - COGNITIVE FUNCTIONS

KW - SERUM TRYPTOPHAN

KW - RECOGNITION

KW - MOOD

KW - POLYMORPHISM

KW - DEPRESSION

KW - VOLUNTEERS

U2 - 10.1007/s00213-008-1201-0

DO - 10.1007/s00213-008-1201-0

M3 - Article

SN - 0033-3158

VL - 200

SP - 243

EP - 254

JO - Psychopharmacology

JF - Psychopharmacology

IS - 2

ER -

Acute tryptophan depletion dose dependently impairs object memory in serotonin transporter knockout rats

Abstract

Keywords

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