+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Characterization of the serotonin transporter knockout rat: a selective change in the functioning of the serotonergic system

, : Characterization of the serotonin transporter knockout rat: a selective change in the functioning of the serotonergic system. Neuroscience 146(4): 1662-1676

Serotonergic signaling is involved in many neurobiological processes and disturbed 5-HT homeostasis is implicated in a variety of psychiatric and addictive disorders. Here, we describe the functional characterization of the serotonin transporter (SERT) knockout rat model, that is generated by N-ethyl-N-nitrosurea (ENU)-driven target-selected mutagenesis. Biochemical characterization revealed that SERT mRNA and functional protein are completely absent in homozygous knockout (SERT-/-) rats, and that there is a gene dose-dependent reduction in the expression and function of the SERT in heterozygous knockout rats. As a result, 5-HT homeostasis was found to be severely affected in SERT-/- rats: 5-HT tissue levels and depolarization-induced 5-HT release were significantly reduced, and basal extracellular 5-HT levels in the hippocampus were ninefold increased. Interestingly, we found no compensatory changes in in vitro activity of tryptophan hydroxylase and monoamine oxidase, the primary enzymes involved in 5-HT synthesis and degradation, respectively. Similarly, no major adaptations in nonserotonergic systems were found, as determined by dopamine and noradrenaline transporter binding, monoamine tissue levels, and depolarization-induced release of dopamine, noradrenaline, glutamate and GABA. In conclusion, neurochemical changes in the SERT knockout rat are primarily limited to the serotonergic system, making this novel rat model potentially very useful for studying the behavioral and neurobiological consequences of disturbed 5-HT homeostasis.


PMID: 17467186

DOI: 10.1016/j.neuroscience.2007.03.030

Other references

Rhoads, H.; Hoekje, P.; Klein, R.; Olson, J., 1995: Solar radon reduction at six homes in northeast Iowa. Proceedings of the Annual Conference American Solar Energy Society Inc: 5-50

Arnesen, C.; Rothstein, I.Z.; Zupan, J., 2009: Smoking guns for on-shell new physics at the LHC. Using Tevatron bounds we derive upper limits on the LHC Higgs boson production rate assuming that no beyond the standard model (BSM) particles are being produced near their mass shell. A violation of these limits would constitute a smoking gun for...

Timasheva, Y.R.; Nasibullin, T.R.; Mustafina, O.E., 2016: The CXCR2 Gene Polymorphism Is Associated with Stroke in Patients with Essential Hypertension. Hypertension is the major risk factor for stroke, and genetic factors contribute to its development. Inflammation has been hypothesized to be the key link between blood pressure elevation and stroke. We performed an analysis of the association bet...

Connors, M.S.zanne; Malfatti, M., A.; Felton, J., S., 1995: The metabolism and DNA binding of the cooked-food mutagen, 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) in precision-cut rat liver slices. Precision-cut liver slices prepared from Aroclor 1254 pretreated male rats were used to investigate the metabolism of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP). The acetyltransferase and sulfotransferase inhibitors, pentachlorophenol...

Vernon-Wortzel, H.W.rtzel, L., 1989: Privatization: not the only answer. Governments in many developing countries created state-owned enterprises (SOEs) to produce goods or provide services the private sector seemed unwilling or unable to offer. In many cases, SOEs have turned out to be problem children—at best, inef...

Lyons, Romola, 1932: Dermatitis due to contact with orange peel Case report with successful desensitization. Three cases of acquired sensitization to orange peel are reported.

Coope, G.; Angus, R., 1975: An ecological study of a temperate interlude in the middle of the last glaciation, based on fossil Coleoptera from isleworth, Middlesex. Journal of animal ecology: 44 (2) 365-391

Koleck, T.A.; Bender, C.M.; Sereika, S.M.; Brufsky, A.M.; Lembersky, B.C.; McAuliffe, P.F.; Puhalla, S.L.; Rastogi, P.; Conley, Y.P., 2016: Polymorphisms in DNA repair and oxidative stress genes associated with pre-treatment cognitive function in breast cancer survivors: an exploratory study. The purpose of this exploratory candidate gene association study was to examine relationships between polymorphisms in oxidative stress and DNA repair genes and pre-adjuvant therapy cognitive function (CF) in postmenopausal women diagnosed with ea...

Singer, B.; Wray, S.; Miller, T.; Cascione, M.; Gupta, A.; Pardo, G.; Watsky, E.; Hayward, B.; Mercer, B.; Dangond, F., 2012: Patient-rated ease of use and functional reliability of an electronic autoinjector for self-injection of subcutaneous interferon beta-1a for relapsing multiple sclerosis. For patients with multiple sclerosis (MS), electronic autoinjectors may improve convenience and reduce discomfort associated with chronic injections. To assess ease of use, patient satisfaction, and functional reliability of an investigational ele...

Atance Martínez, J.C., 1997: Epidemiologic aspects of the burnout syndrome in hospital personnel. Burnout Syndrome is claimed to be the most probable cause of the lack of motivation suffered by professional health workers nowadays. This suggests that the syndrome may be linked to the high levels of absenteeism from work among this professional...