Cholinergic Receptor Blockade in the VTA Attenuates Cue-Induced Cocaine-Seeking and Reverses the Anxiogenic Effects of Forced Abstinence.
Animals
Anti-Anxiety Agents
/ pharmacology
Anxiety
/ drug therapy
Cholinergic Antagonists
/ pharmacology
Cocaine-Related Disorders
/ drug therapy
Disease Models, Animal
Drug-Seeking Behavior
/ drug effects
Focal Adhesion Kinase 2
Male
Mecamylamine
/ pharmacology
Rats, Sprague-Dawley
Receptors, Cholinergic
/ metabolism
Scopolamine
/ pharmacology
Ventral Tegmental Area
/ drug effects
Anxiety
Mood disorders
Muscarinic acetylcholine receptor
Nicotinic acetylcholine receptor
Relapse
Substance abuse
Journal
Neuroscience
ISSN: 1873-7544
Titre abrégé: Neuroscience
Pays: United States
ID NLM: 7605074
Informations de publication
Date de publication:
10 08 2019
10 08 2019
Historique:
received:
07
03
2019
revised:
31
05
2019
accepted:
19
06
2019
pubmed:
5
7
2019
medline:
10
3
2020
entrez:
5
7
2019
Statut:
ppublish
Résumé
Drug relapse after periods of abstinence is a common feature of substance abuse. Moreover, anxiety and other mood disorders are often co-morbid with substance abuse. Cholinergic receptors in the ventral tegmental area (VTA) are known to mediate drug-seeking and anxiety-related behavior in rodent models. However, it is unclear if overlapping VTA cholinergic mechanisms mediate drug relapse and anxiety-related behaviors associated with drug abstinence. We examined the effects of VTA cholinergic receptor blockade on cue-induced cocaine seeking and anxiety during cocaine abstinence. Male Sprague-Dawley rats were trained to self-administer intravenous cocaine (~0.5 mg/kg/infusion, FR1 schedule) for 10 days, followed by 14 days of forced abstinence. VTA infusion of the non-selective nicotinic acetylcholine receptor antagonist mecamylamine (0, 10, and 30 μg/side) or the non-selective muscarinic receptor antagonist scopolamine (0, 2.4 and 24 μg /side) significantly decreased cue-induced cocaine seeking. In cocaine naïve rats, VTA mecamylamine or scopolamine also led to dose-dependent increases in open arm time in the elevated plus maze (EPM). In contrast, rats that received I.V. cocaine, compared to received I.V. saline rats, displayed an anxiogenic response on day 14 of abstinence as reflected by decreased open arm time in the EPM. Furthermore, low doses of VTA mecamylamine (10 μg /side) or scopolamine (2.4 μg /side), that did not alter EPM behavior in cocaine naive rats, were sufficient to reverse the anxiogenic effects of cocaine abstinence. Together, these data point to an overlapping role of VTA cholinergic mechanisms to regulate relapse and mood disorder-related responses during cocaine abstinence.
Identifiants
pubmed: 31271832
pii: S0306-4522(19)30445-2
doi: 10.1016/j.neuroscience.2019.06.028
pmc: PMC6661179
mid: NIHMS1533315
pii:
doi:
Substances chimiques
Anti-Anxiety Agents
0
Cholinergic Antagonists
0
Receptors, Cholinergic
0
Mecamylamine
6EE945D3OK
Scopolamine
DL48G20X8X
Focal Adhesion Kinase 2
EC 2.7.10.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
252-263Subventions
Organisme : NIGMS NIH HHS
ID : R25 GM104553
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH014276
Pays : United States
Informations de copyright
Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.
Références
Neuropsychopharmacology. 2014 May;39(6):1527-37
pubmed: 24395021
J Comp Neurol. 2013 Sep 1;521(13):2927-46
pubmed: 23504804
Pharmacol Biochem Behav. 2006 Sep;85(1):206-13
pubmed: 16987545
J Psychopharmacol. 2009 Sep;23(7):797-804
pubmed: 18583432
Nature. 1998 Jan 8;391(6663):173-7
pubmed: 9428762
Neuropharmacology. 2013 Dec;75:9-18
pubmed: 23850572
J Pharmacol Exp Ther. 1996 Aug;278(2):490-502
pubmed: 8768696
Psychopharmacology (Berl). 2012 Sep;223(2):179-90
pubmed: 22526535
Neuroscience. 2007 Feb 23;144(4):1209-18
pubmed: 17184925
Curr Opin Neurobiol. 2013 Aug;23(4):649-54
pubmed: 23764204
Behav Brain Res. 2015 Jul 15;288:54-62
pubmed: 25865152
Front Pharmacol. 2019 Feb 14;10:72
pubmed: 30837868
Psychopharmacology (Berl). 2007 Dec;195(3):333-43
pubmed: 17703283
Front Pharmacol. 2018 Jan 04;8:924
pubmed: 29354053
Behav Brain Res. 2014 Apr 1;262:42-6
pubmed: 24412684
Cell Rep. 2018 May 22;23(8):2236-2244
pubmed: 29791835
Neurosci Biobehav Rev. 2016 Jun;65:341-61
pubmed: 27095547
J Pharmacol Exp Ther. 2004 Oct;311(1):80-91
pubmed: 15178698
J Neurosci. 2008 Sep 3;28(36):9021-9
pubmed: 18768696
Synapse. 1991 Sep;9(1):60-5
pubmed: 1796352
Neuropsychopharmacology. 2018 Sep;43(10):2118-2125
pubmed: 29472646
Nature. 2003 Apr 10;422(6932):614-8
pubmed: 12687000
Psychopharmacology (Berl). 2008 Jan;195(4):591-603
pubmed: 17899015
Nature. 2013 Jan 24;493(7433):537-541
pubmed: 23235822
Annu Rev Neurosci. 2006;29:565-98
pubmed: 16776597
Neuropsychopharmacology. 1999 Mar;20(3):297-307
pubmed: 10063490
Addict Biol. 2018 Mar;23(2):556-568
pubmed: 28429835
J Clin Psychiatry. 2006 Feb;67(2):247-57
pubmed: 16566620
Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3573-8
pubmed: 23401542
Curr Opin Neurobiol. 2019 Feb;54:66-72
pubmed: 30237117
Prog Neuropsychopharmacol Biol Psychiatry. 2007 Jun 30;31(5):1119-29
pubmed: 17513029
Proc Natl Acad Sci U S A. 1990 Sep;87(18):7050-4
pubmed: 2402490
J Neurosci. 2002 Oct 15;22(20):8785-9
pubmed: 12388584
Behav Brain Res. 2012 May 16;231(1):116-23
pubmed: 22374255
Behav Pharmacol. 2009 May;20(3):286-95
pubmed: 19404193
Alcohol Clin Exp Res. 2010 Mar 1;34(3):396-403
pubmed: 20028366
Ann N Y Acad Sci. 1992 Jun 28;654:513-6
pubmed: 1632615
J Neurosci. 2001 Nov 1;21(21):8655-63
pubmed: 11606653
Eur Psychiatry. 2015 Jan;30(1):128-36
pubmed: 24630346
Neuropsychopharmacology. 2018 Jun;43(7):1510-1517
pubmed: 29483658
Neuropsychopharmacology. 2008 Aug;33(9):2158-66
pubmed: 18033235
Brain Res Bull. 2008 Jul 1;76(4):402-11
pubmed: 18502317
Science. 1980 Sep 26;209(4464):1545-6
pubmed: 7433977
Behav Brain Res. 2017 Jun 30;329:20-25
pubmed: 28442362
J Reward Defic Syndr. 2015;1(3):95-104
pubmed: 27398406
Neuropsychopharmacology. 2018 Nov;43(12):2361-2372
pubmed: 29773910
Eur J Neurosci. 2016 Oct;44(7):2446-2454
pubmed: 27453431
PLoS One. 2012;7(8):e43535
pubmed: 22916276
J Dual Diagn. 2017 Oct-Dec;13(4):298-304
pubmed: 29120266
Behav Brain Res. 2015 Sep 15;291:372-376
pubmed: 26026787
Neuropsychopharmacology. 2016 May;41(6):1579-87
pubmed: 26471256
J Neurosci. 2014 Feb 26;34(9):3253-62
pubmed: 24573284
J Neurosci. 2005 Sep 7;25(36):8141-9
pubmed: 16148222
Science. 2014 Apr 18;344(6181):313-9
pubmed: 24744379
Drug Alcohol Depend. 2018 Jun 1;187:242-248
pubmed: 29684892
Psychopharmacology (Berl). 2006 May;186(1):113-21
pubmed: 16525855
J Neurosci Res. 2003 Oct 1;74(1):91-6
pubmed: 13130510
Behav Pharmacol. 2002 Sep;13(5-6):379-88
pubmed: 12394414
Neurosci Lett. 2016 Mar 11;616:80-5
pubmed: 26828299
Neurosci Lett. 1990 Jul 3;114(2):154-9
pubmed: 2395528
Science. 1991 Mar 29;251(5001):1580-6
pubmed: 2011738
Nature. 2013 Jan 24;493(7433):532-6
pubmed: 23235832
Psychopharmacology (Berl). 2011 Nov;218(1):69-82
pubmed: 21494792
Addict Biol. 2018 Sep;23(5):1106-1116
pubmed: 29044937
Brain Res. 1995 Mar 27;675(1-2):89-97
pubmed: 7796157
Psychopharmacology (Berl). 2013 Sep;229(1):73-82
pubmed: 23624852
J Neurosci. 2006 Jun 14;26(24):6583-8
pubmed: 16775146
J Clin Invest. 2016 Jul 1;126(7):2482-94
pubmed: 27270172
Am J Psychiatry. 1999 Jan;156(1):11-8
pubmed: 9892292
J Neurosci. 2002 Apr 15;22(8):3269-76
pubmed: 11943828
J Neurosci. 2001 Mar 1;21(5):1452-63
pubmed: 11222635
Drug Alcohol Depend. 2010 Jan 1;106(1):21-7
pubmed: 19726138
Neuron. 2006 Jun 15;50(6):911-21
pubmed: 16772172
Biol Psychiatry. 2013 Nov 15;74(10):742-9
pubmed: 23751205
Eur J Neurosci. 2009 Oct;30(7):1358-69
pubmed: 19788581
Arch Gen Psychiatry. 2006 Oct;63(10):1121-9
pubmed: 17015814
Neuropsychopharmacology. 2010 Nov;35(12):2479-88
pubmed: 20736989
Nat Neurosci. 2005 Nov;8(11):1437-9
pubmed: 16251983
J Neurochem. 2008 Oct;107(2):570-7
pubmed: 18717814
PLoS One. 2011;6(11):e27538
pubmed: 22102904
Mol Psychiatry. 2019 May;24(5):694-709
pubmed: 30120418
Neuropharmacology. 2014 Apr;79:573-9
pubmed: 24467849
Br J Pharmacol. 2018 Jun;175(11):1903-1914
pubmed: 28264149
Psychopharmacol Bull. 1980 Oct;16(4):29-31
pubmed: 7454928