PMID- 26472268
OWN - NLM
STAT- MEDLINE
DCOM- 20171012
LR  - 20210109
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 173
IP  - 13
DP  - 2016 Jul
TI  - High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like 
      behavior in mice.
PG  - 2095-110
LID - 10.1111/bph.13343 [doi]
AB  - BACKGROUND AND PURPOSE: The link between type 2 diabetes mellitus (T2DM) and 
      depression is bidirectional. However, the possibility that metabolic disorders 
      may elicit anxiogenic-like/depressive-like symptoms or alter the efficacy of 
      antidepressant drugs remains poorly documented. This study explored the influence 
      of T2DM on emotionality and proposed a therapeutic strategy that might be used in 
      depressed diabetic patients. EXPERIMENTAL APPROACH: Mice were fed a high-fat diet 
      (HFD) and subjected to a full comprehensive metabolic and behavioural analysis to 
      establish correlations between metabolic and psychiatric disorders. In vivo 
      intra-hippocampal microdialysis was also applied to propose a mechanism 
      underpinning the phenotype of mice fed the HFD. Finally, we tested whether 
      chronic administration of the selective 5-HT reuptake inhibitor escitalopram or 
      HFD withdrawal could reverse HFD-induced metabolic and behavioural anomalies. KEY 
      RESULTS: The increased body weight, hyperglycaemia and impaired glucose tolerance 
      in response to HFD were correlated with anxiogenic-like/depressive-like symptoms. 
      Moreover, this phenotype was associated with decreased extracellular 5-HT levels 
      in the hippocampus which may result from increased sensitivity of the dorsal 
      raphe 5-HT1A autoreceptor. Interestingly, the beneficial effect of prolonged 
      administration of escitalopram was abolished in HFD-fed mice. On the contrary, 
      HFD withdrawal completely reversed metabolic impairments and positively changed 
      symptoms of anxiety, although some behavioural anomalies persisted. CONCLUSIONS 
      AND IMPLICATIONS: Our data provide clear-cut evidence that both pathologies are 
      finely correlated and associated with impaired 5-HT mediated neurotransmission in 
      the hippocampus. Further experiments are warranted to define the most adequate 
      strategy for the treatment of such co-morbidity. LINKED ARTICLES: This article is 
      part of a themed section on Updating Neuropathology and Neuropharmacology of 
      Monoaminergic Systems. To view the other articles in this section visit 
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc.
CI  - (c) 2015 The British Pharmacological Society.
FAU - Zemdegs, Juliane
AU  - Zemdegs J
AD  - Faculte de Pharmacie, Universite Paris Sud XI, Chatenay-Malabry, Cedex, France.
AD  - Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la 
      Cognition Animale (CRCA) UMR5169, Toulouse, France.
AD  - UPS CRCA UMR5169, Universite de Toulouse, Toulouse, France.
AD  - Center des Sciences du Gout et de l'Alimentation, UMR 6265 CNRS 1324 INRA, 
      Universite de Bourgogne Franche-Comte, Dijon, France.
FAU - Quesseveur, Gael
AU  - Quesseveur G
AD  - Faculte de Pharmacie, Universite Paris Sud XI, Chatenay-Malabry, Cedex, France.
FAU - Jarriault, David
AU  - Jarriault D
AD  - Center des Sciences du Gout et de l'Alimentation, UMR 6265 CNRS 1324 INRA, 
      Universite de Bourgogne Franche-Comte, Dijon, France.
FAU - Penicaud, Luc
AU  - Penicaud L
AD  - Center des Sciences du Gout et de l'Alimentation, UMR 6265 CNRS 1324 INRA, 
      Universite de Bourgogne Franche-Comte, Dijon, France.
FAU - Fioramonti, Xavier
AU  - Fioramonti X
AD  - Center des Sciences du Gout et de l'Alimentation, UMR 6265 CNRS 1324 INRA, 
      Universite de Bourgogne Franche-Comte, Dijon, France.
FAU - Guiard, Bruno P
AU  - Guiard BP
AD  - Faculte de Pharmacie, Universite Paris Sud XI, Chatenay-Malabry, Cedex, France.
AD  - Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la 
      Cognition Animale (CRCA) UMR5169, Toulouse, France.
AD  - UPS CRCA UMR5169, Universite de Toulouse, Toulouse, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151209
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0DHU5B8D6V (Citalopram)
RN  - 333DO1RDJY (Serotonin)
SB  - IM
MH  - Animals
MH  - Anxiety/drug therapy/metabolism/*physiopathology
MH  - *Behavior, Animal/drug effects
MH  - Citalopram/administration & dosage/pharmacology
MH  - Diet, High-Fat/*adverse effects
MH  - Male
MH  - Metabolic Diseases/drug therapy/metabolism/*physiopathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Serotonin/*metabolism
PMC - PMC4908198
EDAT- 2015/10/17 06:00
MHDA- 2017/10/13 06:00
PMCR- 2017/07/01
CRDT- 2015/10/17 06:00
PHST- 2015/04/22 00:00 [received]
PHST- 2015/09/03 00:00 [revised]
PHST- 2015/09/09 00:00 [accepted]
PHST- 2015/10/17 06:00 [entrez]
PHST- 2015/10/17 06:00 [pubmed]
PHST- 2017/10/13 06:00 [medline]
PHST- 2017/07/01 00:00 [pmc-release]
AID - BPH13343 [pii]
AID - 10.1111/bph.13343 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2016 Jul;173(13):2095-110. doi: 10.1111/bph.13343. Epub 2015 Dec 
      9.