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.

journal_title

Psychopharmacology

authors

Olivier JD,Jans LA,Korte-Bouws GA,Korte SM,Deen PM,Cools AR,Ellenbroek BA,Blokland A

doi

10.1007/s00213-008-1201-0

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

243-54

issue

2

eissn

0033-3158

issn

1432-2072

journal_volume

200

pub_type

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