Blockade of orexin receptors in the infralimbic cortex prevents stress-induced reinstatement of alcohol-seeking behaviour in alcohol-dependent rats.
Hcrtr1
Hcrtr2
TCS 1102
alcohol
dual orexin receptor antagonist
orexin
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
revised:
13
12
2022
received:
21
06
2022
accepted:
14
12
2022
pmc-release:
01
06
2024
medline:
3
5
2023
pubmed:
21
12
2022
entrez:
20
12
2022
Statut:
ppublish
Résumé
A major problem managing alcohol use disorder is the high vulnerability to relapse, even after long periods of abstinence. Chronic alcohol use dysregulates stress responsivity, rendering this system hyporesponsive and making individuals vulnerable to relapse. Orexin (hypocretin) plays a role in diverse physiological processes, including stress. Orexin neurons in the hypothalamus, project to the infralimbic cortex. This study asked does infralimbic cortex orexin transmission play a significant role in stress-induced reinstatement of alcohol-seeking behaviour in alcohol-dependent rats. Male and female rats were trained to self-administer 10% alcohol (3 weeks) and then made dependent via chronic intermittent alcohol vapour exposure. Following extinction (5 days·week TCS 1102 prevented reinstatement in dependent animals only. Moreover, Hcrtr mRNA expression in the hypothalamus and Hcrtr1/2 in the infralimbic cortex increased in alcohol-dependent animals at the time of testing. Dependence dampened basal orexin/OX receptor influence over infralimbic cortex GABAergic synapses (using TCS 1102) allow for greater stimulated orexin effects. Infralimbic cortex transmission is implicate in stress-induced reinstatement of alcohol-seeking behaviour in subjects with a history of alcohol dependence and show maladaptive recruitment of infralimbic cortex transmission by alcohol dependence.
Sections du résumé
BACKGROUND AND PURPOSE
A major problem managing alcohol use disorder is the high vulnerability to relapse, even after long periods of abstinence. Chronic alcohol use dysregulates stress responsivity, rendering this system hyporesponsive and making individuals vulnerable to relapse. Orexin (hypocretin) plays a role in diverse physiological processes, including stress. Orexin neurons in the hypothalamus, project to the infralimbic cortex. This study asked does infralimbic cortex orexin transmission play a significant role in stress-induced reinstatement of alcohol-seeking behaviour in alcohol-dependent rats.
EXPERIMENTAL APPROACH
Male and female rats were trained to self-administer 10% alcohol (3 weeks) and then made dependent via chronic intermittent alcohol vapour exposure. Following extinction (5 days·week
KEY RESULTS
TCS 1102 prevented reinstatement in dependent animals only. Moreover, Hcrtr mRNA expression in the hypothalamus and Hcrtr1/2 in the infralimbic cortex increased in alcohol-dependent animals at the time of testing. Dependence dampened basal orexin/OX receptor influence over infralimbic cortex GABAergic synapses (using TCS 1102) allow for greater stimulated orexin effects.
CONCLUSION AND IMPLICATIONS
Infralimbic cortex transmission is implicate in stress-induced reinstatement of alcohol-seeking behaviour in subjects with a history of alcohol dependence and show maladaptive recruitment of infralimbic cortex transmission by alcohol dependence.
Identifiants
pubmed: 36537731
doi: 10.1111/bph.16015
pmc: PMC10577928
mid: NIHMS1934850
doi:
Substances chimiques
Orexin Receptors
0
Orexins
0
Ethanol
3K9958V90M
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1500-1515Subventions
Organisme : NIAAA NIH HHS
ID : R01 AA027700
Pays : United States
Organisme : NIAAA NIH HHS
ID : F32 AA026765
Pays : United States
Organisme : NIAAA NIH HHS
ID : R00 AA025408
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA028549
Pays : United States
Organisme : NIAAA NIH HHS
ID : T32 AA007456
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA017447
Pays : United States
Organisme : NIAAA NIH HHS
ID : P60 AA006420
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA021491
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA026999
Pays : United States
Informations de copyright
© 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Références
J Neurosci. 1999 Oct 15;19(20):RC35
pubmed: 10516337
Brain Res. 2010 Feb 16;1314:91-102
pubmed: 19748490
Addict Biol. 2018 Jan;23(1):6-15
pubmed: 27558790
Biotechnol Bioeng. 2003 Dec 30;84(7):834-41
pubmed: 14708124
J Neurosci. 2021 Apr 7;41(14):3120-3141
pubmed: 33593856
Psychopharmacology (Berl). 2013 Mar;226(1):155-65
pubmed: 23096770
Behav Brain Res. 2014 Aug 1;269:61-5
pubmed: 24746488
Annu Rev Pharmacol Toxicol. 2011;51:243-66
pubmed: 21034217
Alcohol Clin Exp Res. 2015 Jan;39(1):21-9
pubmed: 25623402
Nature. 2005 Sep 22;437(7058):556-9
pubmed: 16100511
Biotechnol Bioeng. 2003 Dec 30;84(7):822-33
pubmed: 14708123
J Comp Neurol. 2003 Sep 15;464(2):220-37
pubmed: 12898614
Cell. 1998 Mar 6;92(5):1 page following 696
pubmed: 9527442
J Neurosci Res. 2000 Oct 15;62(2):161-8
pubmed: 11020209
Neuropharmacology. 2015 Dec;99:735-49
pubmed: 26188147
Alcohol Alcohol. 2018 Nov 01;53(6):642-649
pubmed: 29309503
Addict Biol. 2016 May;21(3):603-12
pubmed: 25899624
Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):9472-7
pubmed: 26170333
Curr Psychiatry Rep. 2007 Oct;9(5):388-95
pubmed: 17915078
Psychopharmacology (Berl). 2011 May;215(1):191-203
pubmed: 21181123
Biol Psychiatry. 2010 May 1;67(9):804-11
pubmed: 20189165
Biol Psychiatry. 2017 Apr 1;81(7):606-615
pubmed: 27567312
Neurosci Biobehav Rev. 2010 Nov;35(2):276-84
pubmed: 19932711
J Comp Neurol. 2001 Apr 9;432(3):307-28
pubmed: 11246210
Alcohol Clin Exp Res. 2005 Feb;29(2):185-95
pubmed: 15714042
Neuropharmacology. 2018 May 1;133:470-480
pubmed: 29471053
Front Neuroendocrinol. 2018 Oct;51:132-145
pubmed: 29932958
Psychopharmacology (Berl). 2008 Jul;199(1):109-17
pubmed: 18470506
Psychopharmacology (Berl). 2007 Aug;193(2):283-94
pubmed: 17437087
J Neurosci. 2004 Dec 15;24(50):11439-48
pubmed: 15601950
Brain Res. 2010 Feb 16;1314:145-61
pubmed: 20026088
Neuropsychopharmacology. 1999 Sep;21(3):435-44
pubmed: 10457541
Synapse. 2004 Jan;51(1):32-58
pubmed: 14579424
Neuron. 2008 Jul 10;59(1):11-34
pubmed: 18614026
Behav Brain Res. 2012 Jul 15;233(1):224-31
pubmed: 22579972
Brain Res. 2011 May 19;1391:54-9
pubmed: 21439948
J Pharmacol Exp Ther. 2003 May;305(2):507-14
pubmed: 12606634
Psychopharmacology (Berl). 2000 Jun;150(3):317-24
pubmed: 10923760
Addict Biol. 2015 May;20(3):469-81
pubmed: 24712379
Biol Psychiatry. 2012 Feb 1;71(3):214-23
pubmed: 21831361
Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):322-7
pubmed: 9419374
Psychopharmacology (Berl). 1998 Jan;135(2):169-74
pubmed: 9497022
Alcohol Alcohol. 2021 Aug 30;56(5):581-588
pubmed: 33912894
J Neurosci. 2005 Jun 1;25(22):5389-96
pubmed: 15930388
Front Integr Neurosci. 2020 Nov 10;14:599710
pubmed: 33240054
J Comp Neurol. 2005 Nov 14;492(2):145-77
pubmed: 16196030
Psychopharmacology (Berl). 2006 Mar;185(1):19-28
pubmed: 16374599
Cold Spring Harb Perspect Med. 2012 Jun;2(6):a012880
pubmed: 22675669
Sci Adv. 2019 Sep 25;5(9):eaax4043
pubmed: 31579824
Addict Biol. 2014 Mar;19(2):233-6
pubmed: 22830647
Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7698-702
pubmed: 8052645
J Comp Neurol. 2001 Jun 18;435(1):6-25
pubmed: 11370008
Alcohol Clin Exp Res. 2004 Nov;28(11):1676-82
pubmed: 15547454
Brain Res. 2015 Dec 2;1628(Pt A):130-46
pubmed: 25529632
Behav Brain Res. 2014 Oct 1;272:93-9
pubmed: 24983661
Alcohol. 2014 May;48(3):277-86
pubmed: 24290310
J Neurosci. 2006 Sep 27;26(39):9967-74
pubmed: 17005860
Neuropharmacology. 2022 Jun 1;210:109046
pubmed: 35341789
Br J Pharmacol. 2021 Oct;178 Suppl 1:S27-S156
pubmed: 34529832
Acta Physiol (Oxf). 2010 Mar;198(3):303-12
pubmed: 20070282
Neuroreport. 2000 Jun 26;11(9):1939-43
pubmed: 10884047
Neuropsychopharmacology. 2013 Aug;38(9):1724-36
pubmed: 23518606
Alcohol. 2009 Aug;43(5):379-86
pubmed: 19671464
PLoS One. 2012;7(9):e44726
pubmed: 23028593
Annu Rev Neurosci. 2012;35:203-25
pubmed: 22443509
BMJ Open Sci. 2020 Jul 20;4(1):e100115
pubmed: 34095516
Neuropharmacology. 2020 May 15;168:107752
pubmed: 31476352
Neuron. 2006 Feb 16;49(4):589-601
pubmed: 16476667
Brain Res. 2017 Jan 1;1654(Pt A):34-42
pubmed: 27771284
J Neurosci. 1998 Dec 1;18(23):9996-10015
pubmed: 9822755
Alcohol Clin Exp Res. 2010 May;34(5):886-96
pubmed: 20331576
Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12;363(1507):3147-58
pubmed: 18640921
Neuropharmacology. 2009;56 Suppl 1:107-11
pubmed: 18694770
Alcohol Clin Exp Res. 1996 Oct;20(7):1289-98
pubmed: 8904984
Neuropsychopharmacology. 2018 Apr;43(5):1010-1020
pubmed: 29052613
Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2053-8
pubmed: 12566570
Behav Brain Res. 2011 Mar 1;217(2):446-53
pubmed: 20920531
Curr Opin Neurobiol. 2002 Jun;12(3):339-45
pubmed: 12049942
Neurotox Res. 2008 Oct;14(2-3):185-9
pubmed: 19073425
Handb Clin Neurol. 2014;125:33-54
pubmed: 25307567
Life Sci. 2003 Jun 27;73(6):759-68
pubmed: 12801597
Alcohol. 1996 Mar-Apr;13(2):163-70
pubmed: 8814651
J Neurosci. 2018 Apr 4;38(14):3507-3519
pubmed: 29483279
Br J Pharmacol. 2006 Jul;148(6):752-9
pubmed: 16751790
Front Behav Neurosci. 2015 Jun 16;9:161
pubmed: 26136671
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):748-53
pubmed: 9892705
Front Neurosci. 2014 Feb 25;8:33
pubmed: 24616657
Alcohol Res. 2012;34(4):468-83
pubmed: 23584113
JAMA Psychiatry. 2015 Aug;72(8):757-66
pubmed: 26039070