Lipopolysaccharide increases degradation of central monoamines: an in vivo microdialysis study in the nucleus accumbens and medial prefrontal cortex of mice.
European Journal of Pharmacology. 2014-02-01; 725: 55-63
DOI: 10.1016/j.ejphar.2014.01.014
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1. Eur J Pharmacol. 2014 Feb 15;725:55-63. doi: 10.1016/j.ejphar.2014.01.014. Epub
2014 Jan 17.
Lipopolysaccharide increases degradation of central monoamines: an in vivo
microdialysis study in the nucleus accumbens and medial prefrontal cortex of
mice.
van Heesch F(1), Prins J(2), Konsman JP(3), Korte-Bouws GA(2), Westphal KG(2),
Rybka J(2), Olivier B(2), Kraneveld AD(2), Korte SM(2).
Author information:
(1)Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences
(UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG
Utrecht, The Netherlands. Electronic address: .
(2)Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences
(UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG
Utrecht, The Netherlands.
(3)Psychoneuroimmmunology, Nutrition and Genetics, Victor Segalen Bordeaux 2
University, Bordeaux, France.
Peripheral administration of lipopolysaccharide (LPS) in rodents induces
anhedonia, i.e. the inability to experience pleasure. Recently, we reported that
serotonin transporter (SERT) function is required for LPS-induced anhedonia. Less
is known about the effect of LPS on the biological activity of dopamine
transporters (DAT) and norepinephrine transporters (NET). Therefore, in vivo
microdialysis was performed in the nucleus accumbens and medial prefrontal cortex
of C57BL6/J mice exposed to saline or LPS (133 µg/kg i.p.). To investigate the
possible involvement of different monoamine transporters, the triple reuptake
inhibitor DOV 216,303 or saline was i.p. injected 30 min before the saline/LPS
injection. The dose of LPS, shown to decrease responding for brain stimulation
reward in mice, significantly increased extracellular levels of monoamine
metabolites (5-HIAA, DOPAC and HVA) in the nucleus accumbens and medial
prefrontal cortex. Remarkably, DOV 216,303 abolished LPS-induced DOPAC and HVA
formation in the nucleus accumbens, suggesting that LPS increases DAT activity in
this brain area. DOV 216,303 also inhibited LPS-induced DOPAC and HVA formation
in the medial prefrontal cortex. Since DAT density is very low in this brain
structure, reuptake of DA predominantly takes place via NET, suggesting that LPS
increases DAT and NET activity in the medial prefrontal cortex. Furthermore, DOV
216,303 pretreatment prevented LPS-induced 5-HIAA formation only in the medial
prefrontal cortex, indicating that LPS increases prefrontal SERT activity. In
conclusion, the present findings suggest that peripheral LPS increases DAT
activity in the nucleus accumbens and increases NET and SERT activity in the
medial prefrontal cortex of mice.
Copyright © 2014 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.ejphar.2014.01.014
PMID: 24444442 [Indexed for MEDLINE]