Lipopolysaccharide increases degradation of central monoamines: an in vivo microdialysis study in the nucleus accumbens and medial prefrontal cortex of mice.
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.
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands. Electronic address: F.vanHeesch@uu.nl.
Floor
F
van Heesch
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Jolanda
J
Prins
Psychoneuroimmmunology, Nutrition and Genetics, Victor Segalen Bordeaux 2 University, Bordeaux, France.
Jan Pieter
JP
Konsman
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Gerdien A H
GA
Korte-Bouws
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Koen G C
KG
Westphal
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Joanna
J
Rybka
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Berend
B
Olivier
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Aletta D
AD
Kraneveld
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Faculty of Science, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
S Mechiel
SM
Korte
D000818:Animals; D001372:Aza Compounds / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000037:antagonists & inhibitors; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
C474071:1-(3,4-dichlorophenyl)-3-azabicyclo-(3.1.0)hexane hydrochloride; D001372:Aza Compounds; D015306:Biogenic Monoamines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008070:Lipopolysaccharides; D050480:Plasma Membrane Neurotransmitter Transport Proteins
Dopamine transporter; Lipopolysaccharide; Microdialysis; Norepinephrine transporter; Serotonin transporter; Triple reuptake inhibitor