Age- and Sex-Specific Plasticity in Dopamine Transporter Function Revealed by Food Restriction and Exercise in a Rat Activity-Based Anorexia Paradigm.
Journal
The Journal of pharmacology and experimental therapeutics
ISSN: 1521-0103
Titre abrégé: J Pharmacol Exp Ther
Pays: United States
ID NLM: 0376362
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
13
06
2019
accepted:
21
08
2019
pubmed:
5
9
2019
medline:
25
4
2020
entrez:
5
9
2019
Statut:
ppublish
Résumé
Eating disorders such as anorexia typically emerge during adolescence, are characterized by engagement in compulsive and detrimental behaviors, and are often comorbid with neuropsychiatric disorders and drug abuse. No effective treatments exist. Moreover, anorexia lacks adolescent animal models, contributing to a poor understanding of underlying age-specific neurophysiological disruptions. To evaluate the contribution of dopaminergic signaling to the emergence of anorexia-related behaviors during the vulnerable adolescent period, we applied an established adult activity-based anorexia (ABA) paradigm (food restriction plus unlimited exercise access for 4 to 5 days) to adult and adolescent rats of both sexes. At the end of the paradigm, measures of plasma volume, blood hormone levels, dopamine transporter (DAT) expression and function, acute cocaine-induced locomotion, and brain water weight were taken. Adolescents were dramatically more affected by the ABA paradigm than adults in all measures. In vivo chronoamperometry and cocaine locomotor responses revealed sex-specific changes in adolescent DAT function after ABA that were independent of DAT expression differences. Hematocrit, insulin, ghrelin, and corticosterone levels did not resemble shifts typically observed in patients with anorexia, though decreases in leptin levels aligned with human reports. These findings are the first to suggest that food restriction in conjunction with excessive exercise sex-dependently and age-specifically modulate DAT functional plasticity during adolescence. The adolescent vulnerability to this relatively short manipulation, combined with blood measures, evidence need for an optimized age-appropriate ABA paradigm with greater face and predictive validity for the study of the pathophysiology and treatment of anorexia. SIGNIFICANCE STATEMENT: Adolescent rats exhibit a distinctive, sex-specific plasticity in dopamine transporter function and cocaine response after food restriction and exercise access; this plasticity is both absent in adults and not attributable to changes in dopamine transporter expression levels. These novel findings may help explain sex differences in vulnerability to eating disorders and drug abuse during adolescence.
Identifiants
pubmed: 31481515
pii: jpet.119.260794
doi: 10.1124/jpet.119.260794
pmc: PMC6795746
doi:
Substances chimiques
Dopamine Plasma Membrane Transport Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
268-277Subventions
Organisme : NIDA NIH HHS
ID : R21 DA038504
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS082145
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s).
Références
Clin Nutr. 1985 May;4(2):81-6
pubmed: 16831711
Science. 2010 Jul 30;329(5991):532
pubmed: 20671181
Biol Psychiatry. 2006 Jun 15;59(12):1151-9
pubmed: 16566899
Neuropsychopharmacology. 2017 Jan;42(1):216-241
pubmed: 27480574
Trends Cogn Sci. 2015 Oct;19(10):558-566
pubmed: 26419496
J Neurosci. 2015 Apr 15;35(15):5990-7
pubmed: 25878272
Hum Mol Genet. 2016 Apr 1;25(7):1370-81
pubmed: 26908623
Eur J Appl Physiol. 2015 Feb;115(2):345-51
pubmed: 25311752
J Pharmacol Exp Ther. 2002 Sep;302(3):1201-11
pubmed: 12183681
Life Sci. 1982 Jun 21;30(25):2207-14
pubmed: 6180276
Psychopharmacologia. 1973;29(4):289-98
pubmed: 4707021
Prz Gastroenterol. 2013;8(6):383-9
pubmed: 24868288
Nat Neurosci. 2008 Dec;11(12):1381-2
pubmed: 18978778
Curr Opin Psychiatry. 2016 Nov;29(6):340-5
pubmed: 27662598
J Neurosci. 2010 Jun 30;30(26):8888-96
pubmed: 20592211
Proc Biol Sci. 2015 Apr 22;282(1805):
pubmed: 25788601
Biol Psychiatry. 2006 Jul 1;60(1):66-73
pubmed: 16125144
Neuropsychopharmacology. 2003 Dec;28(12):2089-101
pubmed: 12902997
Hippocampus. 2014 Dec;24(12):1421-9
pubmed: 24976385
Dig Dis Sci. 2017 Nov;62(11):2977-2981
pubmed: 28932925
Int J Eat Disord. 2013 Nov;46(7):737-46
pubmed: 23853140
Obesity (Silver Spring). 2009 Jun;17(6):1220-5
pubmed: 19282821
Ann Hematol. 2013 May;92(5):605-13
pubmed: 23392575
Neurosci Biobehav Rev. 2003 Jan-Mar;27(1-2):3-18
pubmed: 12732219
Biol Psychiatry. 2005 Oct 15;58(8):651-7
pubmed: 16018979
Clin Neuropharmacol. 2005 Sep-Oct;28(5):228-37
pubmed: 16239763
J Comp Physiol Psychol. 1967 Dec;64(3):414-21
pubmed: 6082873
Int J Neuropsychopharmacol. 2015 Mar 24;18(7):pyv024
pubmed: 25805560
Trends Neurosci. 2013 Feb;36(2):110-20
pubmed: 23333342
Behav Brain Res. 2013 Jan 1;236(1):251-257
pubmed: 22981561
Acta Psychiatr Scand. 2011 Jul;124(1):6-17
pubmed: 21092024
J Adolesc Health. 2014 May;54(5):574-81
pubmed: 24360247
Synapse. 2012 May;66(5):391-407
pubmed: 22213233
Nat Neurosci. 2016 Mar;19(3):479-86
pubmed: 26854803
Int J Eat Disord. 2014 Sep;47(6):610-9
pubmed: 24903034
Biochem Biophys Res Commun. 2002 Feb 8;290(5):1545-50
pubmed: 11820798
Brain Res Dev Brain Res. 1996 Apr 30;92(2):172-81
pubmed: 8738124
J Trace Elem Med Biol. 2019 Mar;52:263-269
pubmed: 30732892
Addict Behav. 2010 May;35(5):392-8
pubmed: 20074863
Pharmacol Biochem Behav. 2009 Sep;93(3):199-211
pubmed: 19136024
J Neural Transm. 1976;38(2):107-22
pubmed: 775021
Curr Protoc Neurosci. 2014 Apr 10;67:9.47.1-9.47.11
pubmed: 24723321
Neurosci Lett. 1994 Aug 1;176(2):259-63
pubmed: 7830960
Child Adolesc Psychiatr Clin N Am. 2015 Jan;24(1):177-96
pubmed: 25455581
Physiol Behav. 2010 Sep 1;101(2):269-76
pubmed: 20566408
Neuropsychopharmacology. 2019 Jul;44(8):1349-1353
pubmed: 31048727
Psychopharmacologia. 1974;38(3):219-30
pubmed: 4423729
Biol Psychiatry. 2008 Aug 1;64(3):252-5
pubmed: 17919459
Psychopharmacology (Berl). 1997 May;131(1):1-8
pubmed: 9181629
Nat Rev Neurosci. 2008 Dec;9(12):947-57
pubmed: 19002191
Am J Psychiatry. 2003 Jun;160(6):1041-52
pubmed: 12777258
Int J Eat Disord. 1994 Jul;16(1):53-60
pubmed: 7920581
Biol Trace Elem Res. 2012 Jun;147(1-3):261-6
pubmed: 22207220
Lancet Psychiatry. 2015 Dec;2(12):1099-111
pubmed: 26514083
Ann N Y Acad Sci. 2008 Mar;1124:111-26
pubmed: 18400927
Elife. 2014 Sep 12;3:e03781
pubmed: 25217530
Psychiatry Res. 2000 May 15;94(2):121-9
pubmed: 10808037
J Neurosci Methods. 2018 Jan 01;293:191-198
pubmed: 28970163
Eur J Endocrinol. 2010 Feb;162(2):235-9
pubmed: 19884263
J Comp Physiol Psychol. 1953 Dec;46(6):429-33
pubmed: 13109066
Arch Gen Psychiatry. 2011 Jul;68(7):724-31
pubmed: 21727255
Pharmacol Biochem Behav. 2006 Apr;83(4):547-53
pubmed: 16643997
Int J Eat Disord. 2010 Nov 1;43(7):577-83
pubmed: 19728374
Int J Eat Disord. 2003 Mar;33(2):136-42
pubmed: 12616579
Nat Rev Neurosci. 2017 Feb 17;18(3):158-171
pubmed: 28209979
Trends Neurosci. 2007 Aug;30(8):375-81
pubmed: 17604133
Eur Child Adolesc Psychiatry. 2010 Mar;19(3):211-26
pubmed: 20033240
Int J Eat Disord. 2013 May;46(4):289-301
pubmed: 23354987
Neurosci Lett. 2003 May 29;343(1):9-12
pubmed: 12749985
Drug Alcohol Depend. 2008 Nov 1;98(1-2):129-35
pubmed: 18585870
Psychopharmacology (Berl). 2014 Apr;231(8):1581-99
pubmed: 24481565
Pharmacol Rep. 2008 Jul-Aug;60(4):561-5
pubmed: 18799826
J Pharmacol Exp Ther. 1999 Apr;289(1):266-77
pubmed: 10087014
Eur Child Adolesc Psychiatry. 2016 Aug;25(8):903-18
pubmed: 26754944
J Neurosci. 2011 Apr 27;31(17):6605-15
pubmed: 21525301
Compr Psychiatry. 2014 Nov;55(8):1773-84
pubmed: 25214371
Biol Psychiatry. 2005 Dec 1;58(11):908-12
pubmed: 15992780
Psychopharmacology (Berl). 2012 Dec;224(3):387-400
pubmed: 22752381
Front Neuroendocrinol. 2014 Jan;35(1):89-110
pubmed: 24184692
Appetite. 2018 Nov 1;130:50-58
pubmed: 30075177
Pharmacol Biochem Behav. 2002 Oct;73(3):663-71
pubmed: 12151042
Ann N Y Acad Sci. 2008;1129:35-46
pubmed: 18591467
Brain Res Bull. 2011 Aug 10;86(1-2):123-8
pubmed: 21741457
Nat Neurosci. 2010 May;13(5):635-41
pubmed: 20348917
Neuropsychiatr Dis Treat. 2013;9:449-61
pubmed: 23579318
Crit Rev Biochem Mol Biol. 2013 Jan-Feb;48(1):1-19
pubmed: 23173916
Neurobiol Stress. 2016 Aug 24;6:78-93
pubmed: 28229111
Psychopharmacology (Berl). 2011 Nov;218(2):357-69
pubmed: 21567123
Brain Res. 2005 Nov 9;1061(2):88-96
pubmed: 16226228
Behav Brain Res. 2002 Dec 2;137(1-2):165-77
pubmed: 12445722
Exp Clin Psychopharmacol. 2012 Dec;20(6):437-46
pubmed: 22924703
World J Biol Psychiatry. 2018 Apr;19(3):225-235
pubmed: 28132573
Neurosci Lett. 1992 May 11;139(1):73-6
pubmed: 1407684
Eat Weight Disord. 2014 Mar;19(1):61-8
pubmed: 24136349