title: Infusion of fluoxetine, a serotonin reuptake inhibitor, in the shell region of the nucleus accumbens increases blood glucose concentrations in rats.
abstract: The brain is well known to regulate blood glucose, and the hypothalamus and hindbrain, in particular, have been studied extensively to understand the underlying mechanisms. Nuclei in these regions respond to alterations in blood glucose concentrations and can alter glucose liver output or glucose tissue uptake to maintain blood glucose concentrations within strict boundaries. Interestingly, several cortico-limbic regions also respond to alterations in glucose concentrations and have been shown to project to hypothalamic nuclei and glucoregulatory organs. For instance, electrical stimulation of the shell of the nucleus accumbens (sNAc) results in increased circulating concentrations of glucose and glucagon and activation of the lateral hypothalamus (LH). Whether this is caused by the simultaneous increase in serotonin release in the sNAc remains to be determined. To study the effect of sNAc serotonin on systemic glucose metabolism, we implanted bilateral microdialysis probes in the sNAc of male Wistar rats and infused fluoxetine, a serotonin reuptake inhibitor, or vehicle after which blood glucose, endogenous glucose production (EGP) and glucoregulatory hormones were measured. Fluoxetine in the sNAc for 1h significantly increased blood glucose concentrations without an effect on glucoregulatory hormones. This increase was accompanied by a higher EGP in the fluoxetine infused rats compared to the controls. These data provide further evidence for a role of sNAc-serotonin in the regulation of glucose metabolism.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Diepenbroek
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Rijnsburger
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Eggels
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: K M
authors.initials: KM
authors.lastname: van Megen
authors.affiliation: Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: M T
authors.initials: MT
authors.lastname: Ackermans
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Kalsbeek
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Serlie
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: s.e.lafleur@amc.uva.nl.
authors.forename: S E
authors.initials: SE
authors.lastname: la Fleur
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D005473:Fluoxetine; D005947:Glucose; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Endogenous glucose production; Glucagon; Glucose; Insulin; Nucleus accumbens shell