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Exploring the effects of tetrahydrobiopterin on motivation, dopamine release and acute inflammation in mice

dc.rights.licenseopenen_US
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorFANET, Hortense
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorOUMMADI, Asma
dc.contributor.authorLO, A.
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorDUCROCQ, Fabien
dc.contributor.authorTOURNISSAC, Marine
dc.contributor.authorBOURASSA, Philippe
dc.contributor.authorMOUSSA, F.
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorCAPURON, Lucile
IDREF: 167018736
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorLAYE, Sophie
ORCID: 0000-0002-3843-1012
IDREF: 11366883X
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
dc.contributor.authorCAILLE GARNIER, Stephanie
ORCID: 0000-0002-4906-3091
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorTRIFILIEFF, Pierre
dc.contributor.authorCALON, Frederic
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorVANCASSEL, Sylvie
dc.date.accessioned2021-09-20T13:14:08Z
dc.date.available2021-09-20T13:14:08Z
dc.date.issued2018-11
dc.date.conference2018-11-03
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112251
dc.description.abstractEnInflammation can affect mesodopaminergic system and mediates depressive symptoms related to motivation and locomotion. Precisely, pro-inflammatory cytokines can alter dopamine synthesis and thus availability. Tetrahydrobiopterin (BH4) is the mandatory co-factor for phenylalanine and tyrosine hydroxylase activities and therefore essential for dopamine synthesis. Interestingly, inflammation can decrease BH4 by acting on its synthesis and degradation. So, lower BH4 level could participate to the dopaminergic and motivational deficits that occur frequently in chronic inflammatory conditions. Despite its importance, the effects of BH4 administration on dopamine synthesis and related behaviors have been poorly characterized. We hypothesized that BH4 administration can improve dopaminergic function and motivational processes and could be used to counteract inflammation-induced alterations. We first demonstrated that peripheral administration of BH4 (50mg/kg;intraperitoneally) was sufficient to double BH4 brain content within 3h. Using in-situ brain perfusion, we found that the brain uptake clearance (Clup) of BH4 was approximately 0.08μl/g/sec, consistent with a modest transfer across the blood brain barrier. BH4 injection neither changed the expression of main enzymes involved in BH4 and DA synthesis nor total striatal dopamine content. However, using in vivo microdialysis in freely moving mice, we showed that BH4 administration induced a slight increase in dopamine release in the nucleus accumbens during food presentation and a higher amphetamine-induced DA release (3mg/kg). Furthermore, BH4 injection increased motivation in a progressive ratio task in operant conditioning without affecting sucrose consumption and anhedonia. Surprisingly, BH4 injection led to a moderate decrease in spontaneous locomotion and to a blunted locomotor sensitization after second exposure to amphetamine. Last, BH4 injection reduced brain pro-inflammatory cytokines expression in an acute inflammation model induced by lLipopolysaccharide injection (830μg/kg). Here, we showed that increased BH4 content leads to increased dopamine release and motivation, and reduces the proinflammatory response to an acute inflammatory challenge. This suggests that BH4 could be a promising treatment for behavioral deficits related to dopaminergic disturbances related to inflammatory condition.
dc.language.isoENen_US
dc.title.enExploring the effects of tetrahydrobiopterin on motivation, dopamine release and acute inflammation in mice
dc.typeCommunication dans un congrès avec actesen_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
bordeaux.hal.laboratoriesNutriNeurO (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINRAEen_US
bordeaux.institutionCNRS
bordeaux.conference.titleNeuroscience 2018en_US
bordeaux.countryusen_US
bordeaux.title.proceedingPoster Presentationsen_US
bordeaux.teamPsychoneuroimmunologie et Nutrition: Approches expérimentales et cliniquesen_US
bordeaux.conference.citySan Diegoen_US
bordeaux.peerReviewedouien_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.date=2018-11&rft.au=FANET,%20Hortense&OUMMADI,%20Asma&LO,%20A.&DUCROCQ,%20Fabien&TOURNISSAC,%20Marine&rft.genre=proceeding


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