title: Leptin reduces food intake via a dopamine D2 receptor-dependent mechanism.
abstract: Food intake is generally accepted to be regulated by the melanocortin system, however recent data suggests that mesolimbic dopaminergic neurons also influence food intake. Whether dopamine signaling is crucial for the acute effect of leptin on feeding is unknown. Using pharmacological and genetic strategies, we tested the hypothesis that the acute inhibitory effect of leptin on food intake is partially mediated by dopamine. Dopamine D2 but not D1 receptor blockade attenuated the acute hypophagic effect of leptin in fasted mice. Additionally, mice lacking the D2R (D2R KO) exhibited an attenuated response to leptin. Conversely, dopamine receptor blockade had no effect on the acute hypophagic effect of melanocortin stimulation or the hyperphagic effect of ghrelin. These findings suggest that dopaminergic pathways do not constitute a normal part of melanocortin-dependent feeding regulation and that the dopaminergic neurocircuitry typically associated with regulation of hedonic feeding likely contributes to feeding regulation by leptin.
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
authors.forename: Sonja K
authors.initials: SK
authors.lastname: Billes
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Simonds
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cowley
keywords: Dopamine; Food intake; Hypothalamus; Leptin; Melanocortin system; Mesolimbic dopamine system
references.citation: Biol Psychiatry. 2011 Apr 1;69(7):668-74
references.pmid: 21035790
references.citation: J Neurosci. 2011 Aug 24;31(34):12189-97
references.pmid: 21865462
references.citation: Neuron. 1998 Dec;21(6):1375-85
references.pmid: 9883730
references.citation: Lancet. 2001 Feb 3;357(9253):354-7
references.pmid: 11210998
references.citation: J Neurosci. 2002 May 1;22(9):3306-11
references.pmid: 11978804
references.citation: Neuron. 2006 Sep 21;51(6):811-22
references.pmid: 16982425
references.citation: Behav Pharmacol. 1994 Oct;5(6):615-622
references.pmid: 11224241
references.citation: Eur J Pharmacol. 2003 Nov 7;480(1-3):125-31
references.pmid: 14623356
references.citation: J Clin Endocrinol Metab. 2006 Aug;91(8):3236-40
references.pmid: 16705078
references.citation: Science. 2007 Sep 7;317(5843):1355
references.pmid: 17690262
references.citation: Neuron. 1997 Jul;19(1):103-13
references.pmid: 9247267
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 Jan;296(1):R9-R19
references.pmid: 18945945
references.citation: Eur J Neurosci. 2005 Apr;21(8):2233-42
references.pmid: 15869520
references.citation: Brain Res. 2003 Feb 21;964(1):107-15
references.pmid: 12573518
references.citation: Endocrinology. 2004 Jun;145(6):2607-12
references.pmid: 14962995
references.citation: Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E1038-43
references.pmid: 16803851
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18276-9
references.pmid: 17986612
references.citation: Behav Neurosci. 1991 Apr;105(2):272-81
references.pmid: 1675060
references.citation: Physiol Behav. 2007 Aug 15;91(5):486-98
references.pmid: 17307205
references.citation: J Nutr. 2009 Mar;139(3):623-8
references.pmid: 19176748
references.citation: Brain Res. 2006 Sep 27;1112(1):169-78
references.pmid: 16925984
references.citation: Nature. 1995 Oct 12;377(6549):530-2
references.pmid: 7566151
references.citation: Nat Genet. 1999 Jan;21(1):119-22
references.pmid: 9916804
references.citation: Cell Metab. 2008 May;7(5):400-9
references.pmid: 18460331
references.citation: J Clin Psychiatry. 2007;68 Suppl 1:20-7
references.pmid: 17286524
references.citation: J Comp Neurol. 2009 Jun 10;514(5):518-32
references.pmid: 19350671
references.citation: Diabetes. 1997 Dec;46(12):2119-23
references.pmid: 9392508
references.citation: Science. 1995 Jul 28;269(5223):543-6
references.pmid: 7624777
references.citation: J Clin Invest. 1996 Sep 1;98(5):1101-6
references.pmid: 8787671
references.citation: Nat Med. 1995 Nov;1(11):1155-61
references.pmid: 7584987
references.citation: Nat Neurosci. 2005 May;8(5):571-8
references.pmid: 15856065
references.citation: J Biol Chem. 2010 Mar 19;285(12):8905-17
references.pmid: 20080963
references.citation: Cell Metab. 2009 Aug;10(2):89-98
references.pmid: 19656487
references.citation: Synapse. 2008 Jan;62(1):50-61
references.pmid: 17960763
references.citation: Neuroimage. 2008 Oct 1;42(4):1537-43
references.pmid: 18598772
references.citation: Endocrinology. 2008 Apr;149(4):1773-85
references.pmid: 18162515
references.citation: Brain Res Brain Res Rev. 1998 Dec;28(3):309-69
references.pmid: 9858756
references.citation: Endocrinology. 2010 Oct;151(10):4745-55
references.pmid: 20826561
references.citation: J Clin Invest. 2006 Dec;116(12):3229-39
references.pmid: 17060947
references.citation: Diabetes. 2010 Feb;59(2):323-9
references.pmid: 20103710
references.citation: Nature. 1994 Dec 1;372(6505):425-32
references.pmid: 7984236
references.citation: Ann Clin Psychiatry. 2003 Mar;15(1):49-58
references.pmid: 12839432
references.citation: Pharmacol Biochem Behav. 2010 Nov;97(1):55-62
references.pmid: 20600253
references.citation: J Clin Invest. 2012 Mar;122(3):1000-9
references.pmid: 22326958
references.citation: Psychopharmacology (Berl). 2004 Aug;174(4):477-89
references.pmid: 15243737
references.citation: Physiol Rev. 1998 Jan;78(1):189-225
references.pmid: 9457173
references.citation: Neuroendocrinology. 2010;92(4):207-14
references.pmid: 20975260
references.citation: Synapse. 2010 Jul;64(7):503-10
references.pmid: 20175225
references.citation: Pharmacol Biochem Behav. 1997 Nov;58(3):631-5
references.pmid: 9329051
references.citation: Nature. 2001 May 24;411(6836):480-4
references.pmid: 11373681
references.citation: Brain Res Mol Brain Res. 1997 Aug;48(1):23-9
references.pmid: 9379845
references.citation: Neuron. 2006 Sep 21;51(6):801-10
references.pmid: 16982424
references.citation: Neuron. 2002 Oct 10;36(2):199-211
references.pmid: 12383777
references.citation: Neuron. 2008 Mar 27;57(6):930-41
references.pmid: 18367093
references.citation: Cell Metab. 2007 Mar;5(3):181-94
references.pmid: 17339026