Effects of insulin and leptin in the ventral tegmental area and arcuate hypothalamic nucleus on food intake and brain reward function in female rats.
There is evidence for a role of insulin and leptin in food intake, but the effects of these adiposity signals on the brain reward system are not well understood. Furthermore, the effects of insulin and leptin on food intake in females are underinvestigated. These studies investigated the role of insulin and leptin in the ventral tegmental area (VTA) and the arcuate hypothalamic nucleus (Arc) on food intake and brain reward function in female rats. The intracranial self-stimulation procedure was used to assess the effects of insulin and leptin on the reward system. Elevations in brain reward thresholds are indicative of a decrease in brain reward function. The bilateral administration of leptin into the VTA (15-500 ng/side) or Arc (15-150 ng/side) decreased food intake for 72 h. The infusion of leptin into the VTA or Arc resulted in weight loss during the first 48 (VTA) or 24 h (Arc) after the infusions. The administration of insulin (0.005-5 mU/side) into the VTA or Arc decreased food intake for 24 h but did not affect body weights. The bilateral administration of low, but not high, doses of leptin (15 ng/side) or insulin (0.005 mU/side) into the VTA elevated brain reward thresholds. Neither insulin nor leptin in the Arc affected brain reward thresholds. These studies suggest that a small increase in leptin or insulin levels in the VTA leads to a decrease in brain reward function. A relatively large increase in insulin or leptin levels in the VTA or Arc decreases food intake.
Department of Psychiatry, McKnight Brain Institute, University of Florida, 100 S. Newell Dr., Gainesville, FL 32610, USA. awbruijn@ufl.edu
Adrie W
AW
Bruijnzeel
Lu W
LW
Corrie
Jessica A
JA
Rogers
Hidetaka
H
Yamada
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D004567:Electrodes, Implanted; D005260:Female; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012653:Self Stimulation; D017557:Ventral Tegmental Area / Q000502:physiology*
D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin
Brain Res. 1992 Oct 16;593(2):314-8
1450939
JAMA. 2010 Jan 20;303(3):235-41
20071471
Annu Rev Neurosci. 1996;19:319-40
8833446
Eur J Clin Nutr. 1995 Feb;49(2):79-90
7743988
J Neurosci Methods. 1980 Dec;3(2):129-49
6110810
Eur J Pharmacol. 2003 Dec 15;482(1-3):185-7
14660021
Nature. 1994 Dec 1;372(6505):425-32
7984236
Int J Eat Disord. 1995 Jul;18(1):79-90
7670446
Neuropsychopharmacology. 1991 Jan;4(1):17-26
2003866
Obstet Gynecol. 1974 Feb;43(2):161-70
4855689
Brain Res. 2003 Feb 21;964(1):107-15
12573518
J Comp Neurol. 1998 Jun 15;395(4):535-47
9619505
Psychopharmacology (Berl). 1989;97(1):89-95
2496433
Behav Neurosci. 1990 Apr;104(2):373-85
2189441
Endocrinology. 1987 Oct;121(4):1562-70
3653038
Behav Neurosci. 2004 Jun;118(3):479-87
15174925
Biol Psychiatry. 2011 Apr 1;69(7):668-74
21035790
Science. 2000 Jan 7;287(5450):125-8
10615045
Nat Neurosci. 2002 Jun;5(6):566-72
12021765
Int J Obes Relat Metab Disord. 2004 Apr;28(4):606-10
14968127
J Clin Invest. 1996 Sep 1;98(5):1101-6
8787671
Annu Rev Psychol. 1989;40:191-225
2648975
Annu Rev Psychol. 2000;51:255-77
10751972
Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7966-9
8367449
Brain Res. 2000 Apr 28;863(1-2):160-8
10773204
Diabetes. 1996 Jul;45(7):984-7
8666153
J Clin Endocrinol Metab. 1998 Nov;83(11):4140-7
9814504
J Clin Invest. 1973 May;52(5):1113-21
4700486
Science. 1998 May 29;280(5368):1378-83
9603721
Physiol Behav. 2006 Nov 30;89(4):611-6
17045623
Endocrinology. 1991 May;128(5):2645-7
2019270
J Nutr. 2009 Mar;139(3):629-32
19176746
Am J Physiol. 1996 Sep;271(3 Pt 2):R766-9
8853402
Neuropharmacology. 2004 Sep;47(4):572-9
15380374
Am J Physiol Endocrinol Metab. 2009 Jul;297(1):E202-10
19435852
Appetite. 1986 Dec;7(4):381-6
3539015
Science. 2004 Apr 2;304(5667):110-5
15064421
Nature. 2000 Apr 6;404(6778):661-71
10766253
Neuropsychopharmacology. 2009 Jun;34(7):1743-52
19145226
Am J Physiol. 1998 Jun;274(6):R1626-38
9608017
J Nutr. 1997 Oct;127(10):2065-72
9311966
Nature. 1979 Nov 29;282(5738):503-5
116135
Endocrinology. 1992 Jun;130(6):3608-16
1597158
Am J Physiol Regul Integr Comp Physiol. 2008 Aug;295(2):R388-94
18525010
Biol Psychiatry. 2006 Mar 1;59(5):477-80
16169528
Fed Proc. 1979 Oct;38(11):2473-6
488370
Science. 1996 Feb 16;271(5251):994-6
8584938
Neurosci Lett. 1997 Mar 21;224(3):149-52
9131658
Neuropharmacology. 2011 Feb-Mar;60(2-3):303-11
20854830
J Pharmacol Exp Ther. 1995 Feb;272(2):781-5
7853194
Neuropsychopharmacology. 2007 Apr;32(4):955-63
16943772
Nutr Rev. 1998 Apr;56(4 Pt 1):106-14
9584495
Nature. 1998 May 7;393(6680):76-9
9590692
Trends Endocrinol Metab. 1993 Sep;4(7):217-24
18407159
Trends Pharmacol Sci. 1992 May;13(5):177-84
1604710
Science. 1997 Oct 3;278(5335):52-8
9311926
Pharmacol Biochem Behav. 2002 May;72(1-2):423-9
11900815
Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10931-5
1961764
Horm Metab Res. 1996 Dec;28(12):664-8
9013738
Endocrinology. 2002 Oct;143(10):3779-84
12239088
Physiol Behav. 1992 Jan;51(1):111-9
1741436
Neurosci Lett. 1998 Feb 27;243(1-3):41-4
9535108
Diabetes. 2003 Mar;52(3):682-7
12606509
Pediatrics. 1999 Mar;103(3):E26
10049982
Am J Physiol Regul Integr Comp Physiol. 2009 Jan;296(1):R9-R19
18945945
Neurosci Lett. 1993 Aug 6;158(1):47-50
8233072
Neuron. 2006 Sep 21;51(6):801-10
16982424
Nature. 1978 Apr 27;272(5656):827-9
205798