RGD Reference Report - A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders. - Rat Genome Database

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A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders.

Authors: Olivier, JD  Van Der Hart, MG  Van Swelm, RP  Dederen, PJ  Homberg, JR  Cremers, T  Deen, PM  Cuppen, E  Cools, AR  Ellenbroek, BA 
Citation: Olivier JD, etal., Neuroscience. 2008 Mar 27;152(3):573-84. Epub 2008 Jan 1.
RGD ID: 4889509
Pubmed: PMID:18295409   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuroscience.2007.12.032   (Journal Full-text)

Human studies have shown that a reduction of 5-HT transporter (SERT) increases the vulnerability for anxiety and depression. Moreover, women are more vulnerable to develop depression and anxiety disorders than men. For that reason we hypothesized that homozygous 5-HT transporter knockout rat (SERT(-/-)) models, especially female, are valuable and reliable animal models for humans with an increased vulnerability for anxiety- and depression-related disorders. As rats are extensively used in neuroscience research, we used the unique 5-HT transporter knockout rat, that was recently generated using N-ethyl-N-nitrosurea (ENU) -driven mutagenesis, to test this hypothesis. Behavioral testing revealed that male and female SERT(-/-) rats spent less time in the center of the open field and spent less time on the open arm of the elevated plus maze compared with wild-type 5-HT transporter knockout rats (SERT(+/+)). In the novelty suppressed feeding test, only male SERT(-/-) rats showed a higher latency before starting to eat in a bright novel arena compared with SERT(+/+) controls. Both male and female SERT(-/-) rats showed a higher escape latency from their home cage than SERT(+/+) littermates. Moreover, SERT(-/-) rats were less mobile in the forced swim test, and sucrose consumption was reduced in SERT(-/-) rats relative to SERT(+/+) rats. Both effects were sex-independent. Neurochemically, basal extracellular 5-HT levels were elevated to a similar extent in male and female SERT(-/-) rats, which was not influenced by the selective 5-HT reuptake inhibitor citalopram. 5-HT immunostaining revealed no difference between SERT(+/+) and SERT(-/-) rats in the dorsal raphe nuclei, in both males and females. These findings demonstrate that SERT(-/-) rats show anxiety and depression-related behavior, independent of sex. Genetic inactivation of the SERT has apparently such a great impact on behavior, that hardly any differences are found between male and female rats. This knockout rat model may provide a valuable model to study anxiety- and depression-related disorders in male and female rats.

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Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
anhedonia  IMP 4889509; 4889509; 4889509compared to wild type littermateRGD 
increased anxiety-related response  IMP 4889509; 4889509; 4889509compared to wild type littermateRGD 
Objects Annotated

Genes (Rattus norvegicus)
Slc6a4  (solute carrier family 6 member 4)
Slc6a4m1Hubr  (solute carrier family 6 member 4; ZFN induced mutant1, Hubr)

Genes (Mus musculus)
Slc6a4  (solute carrier family 6 (neurotransmitter transporter, serotonin), member 4)

Genes (Homo sapiens)
SLC6A4  (solute carrier family 6 member 4)

Strains
WI-Slc6a4m1Hubr-/-  (NA)


Additional Information