Neurotensin receptor 1-biased ligand attenuates neurotensin-mediated excitation of ventral tegmental area dopamine neurons and dopamine release in the nucleus accumbens.
Ventral Tegmental Area
/ metabolism
Dopaminergic Neurons
/ drug effects
Nucleus Accumbens
/ metabolism
Dopamine
/ metabolism
Male
Female
Animals
Mice
Mice, Inbred C57BL
Presynaptic Terminals
/ metabolism
Action Potentials
/ drug effects
Receptors, Neurotensin
/ antagonists & inhibitors
Neurotensin
/ metabolism
Ligands
Dopamine D2 Receptor Antagonists
/ metabolism
D2 autoreceptor
Dopamine
Neurotensin
Neurotensin receptor-1
Nucleus accumbens
Ventral tegmental area
Journal
Neuropharmacology
ISSN: 1873-7064
Titre abrégé: Neuropharmacology
Pays: England
ID NLM: 0236217
Informations de publication
Date de publication:
15 08 2023
15 08 2023
Historique:
received:
02
12
2022
revised:
29
03
2023
accepted:
10
04
2023
pmc-release:
15
08
2024
medline:
17
5
2023
pubmed:
14
4
2023
entrez:
13
4
2023
Statut:
ppublish
Résumé
Strong expression of the G protein-coupled receptor (GPCR) neurotensin receptor 1 (NTR1) in ventral tegmental area (VTA) dopamine (DA) neurons and terminals makes it an attractive target to modulate DA neuron activity and normalize DA-related pathologies. Recent studies have identified a novel class of NTR1 ligand that shows promising effects in preclinical models of addiction. A lead molecule, SBI-0654553 (SBI-553), can act as a positive allosteric modulator of NTR1 β-arrestin recruitment while simultaneously antagonizing NTR1 Gq protein signaling. Using cell-attached recordings from mouse VTA DA neurons we discovered that, unlike neurotensin (NT), SBI-553 did not independently increase spontaneous firing. Instead, SBI-553 blocked the NT-mediated increase in firing. SBI-553 also antagonized the effects of NT on dopamine D2 auto-receptor signaling, potentially through its inhibitory effects on G-protein signaling. We also measured DA release directly, using fast-scan cyclic voltammetry in the nucleus accumbens and observed antagonist effects of SBI-553 on an NT-induced increase in DA release. Further, in vivo administration of SBI-553 did not notably change basal or cocaine-evoked DA release measured in NAc using fiber photometry. Overall, these results indicate that SBI-553 blunts NT's effects on spontaneous DA neuron firing, D2 auto-receptor function, and DA release, without independently affecting these measures. In the presence of NT, SBI-553 has an inhibitory effect on mesolimbic DA activity, which could contribute to its efficacy in animal models of psychostimulant use.
Identifiants
pubmed: 37055008
pii: S0028-3908(23)00134-X
doi: 10.1016/j.neuropharm.2023.109544
pmc: PMC10192038
mid: NIHMS1893083
pii:
doi:
Substances chimiques
Dopamine
VTD58H1Z2X
neurotensin type 1 receptor
0
Receptors, Neurotensin
0
Neurotensin
39379-15-2
Ligands
0
Dopamine D2 Receptor Antagonists
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
109544Subventions
Organisme : BLRD VA
ID : I01 BX005782
Pays : United States
Organisme : NIDA NIH HHS
ID : R00 DA048970
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA036612
Pays : United States
Organisme : BLRD VA
ID : I01 BX003759
Pays : United States
Organisme : NIDA NIH HHS
ID : R33 DA038019
Pays : United States
Informations de copyright
Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Declaration of competing interest US patents 9 868 707 and 10 118 902 relating to the chemistry of SBI-553 and its derivatives have been issued to the Sanford Burnham Prebys Medical Research Institute (A.B·P.) and Duke University (M.G.C., L.S·B.).
Références
CNS Drugs. 2021 Mar;35(3):253-264
pubmed: 33651366
Neuroscience. 2014 Dec 12;282:13-22
pubmed: 24463000
Pharmacol Rev. 2011 Mar;63(1):182-217
pubmed: 21303898
Neuropeptides. 2019 Aug;76:101930
pubmed: 31079844
ACS Chem Biol. 2016 Jul 15;11(7):1880-90
pubmed: 27119457
Neuropharmacology. 2020 May 1;167:108005
pubmed: 32057800
Peptides. 2006 Oct;27(10):2385-404
pubmed: 16891042
Pharmacol Rev. 2001 Dec;53(4):453-86
pubmed: 11734615
J Biol Chem. 2016 Apr 22;291(17):8969-77
pubmed: 26984408
J Neurosci. 2004 Mar 10;24(10):2566-74
pubmed: 15014132
J Neurophysiol. 2015 Sep;114(3):1734-45
pubmed: 26180119
Curr Opin Pharmacol. 2009 Feb;9(1):53-8
pubmed: 19138563
J Pharmacol Exp Ther. 2017 Jun;361(3):341-348
pubmed: 28302862
J Biol Chem. 2011 Mar 18;286(11):9174-84
pubmed: 21233215
J Neurosci. 1992 Jun;12(6):2433-8
pubmed: 1318960
Eur J Neurosci. 2006 Nov;24(10):2789-800
pubmed: 17116165
Behav Sci (Basel). 2014 Jun 13;4(2):125-153
pubmed: 25379273
J Med Chem. 2019 Sep 12;62(17):8357-8363
pubmed: 31390201
J Neurochem. 1991 Jan;56(1):178-83
pubmed: 1824779
Neuroscience. 2000;95(2):417-23
pubmed: 10658621
J Psychopharmacol. 2016 Feb;30(2):112-27
pubmed: 26755548
J Pharmacol Exp Ther. 2002 Jan;300(1):305-13
pubmed: 11752130
Annu Rev Pharmacol Toxicol. 2012;52:179-97
pubmed: 21942629
Neuropeptides. 2018 Apr;68:57-74
pubmed: 29478718
Trends Mol Med. 2011 Mar;17(3):126-39
pubmed: 21183406
J Chem Neuroanat. 1989 Sep-Oct;2(5):253-7
pubmed: 2553068
Peptides. 2006 Oct;27(10):2364-84
pubmed: 16934369
J Comp Neurol. 2001 Jun 25;435(2):142-55
pubmed: 11391637
Eur J Neurosci. 2019 Mar;49(6):784-793
pubmed: 29405480
Curr Opin Neurobiol. 2012 Jun;22(3):545-51
pubmed: 22000687
Brain Res Rev. 2008 Aug;58(2):365-73
pubmed: 18096238
eNeuro. 2018 Feb 12;5(1):
pubmed: 29464190
FEBS J. 2021 Mar;288(5):1462-1474
pubmed: 32702182
J Pharmacol Sci. 2021 Sep;147(1):86-94
pubmed: 34294377
J Neurosci. 2015 Aug 05;35(31):11144-52
pubmed: 26245975
Eur J Pharmacol. 2017 Jun 15;805:1-13
pubmed: 28341345
Neuroscience. 1984 Apr;11(4):919-30
pubmed: 6738859
J Vis Exp. 2018 Feb 26;(132):
pubmed: 29553547
J Neurosci. 2017 Nov 15;37(46):11166-11180
pubmed: 29030431
Brain Res Mol Brain Res. 1997 Mar;44(2):334-40
pubmed: 9073175
BMC Neurosci. 2009 Aug 14;10:96
pubmed: 19682375
Brain Res. 2002 Oct 25;953(1-2):63-72
pubmed: 12384239
J Neurosci. 2022 Aug 10;42(32):6186-6194
pubmed: 35794014
Life Sci. 2003 Jun 27;73(6):679-90
pubmed: 12801589
Neuroscience. 1994 Apr;59(4):921-9
pubmed: 8058127
Nature. 2020 Mar;579(7798):303-308
pubmed: 31945771
Neuroscience. 2002;111(1):177-87
pubmed: 11955721
Front Neurosci. 2015 Nov 05;9:404
pubmed: 26594139
Synapse. 2002 Apr;44(1):15-22
pubmed: 11842442
Brain Res. 1989 May 29;488(1-2):311-27
pubmed: 2545303
Neurochem Res. 1992 Nov;17(11):1143-6
pubmed: 1461361
PLoS One. 2017 Jul 7;12(7):e0180710
pubmed: 28686721
J Psychiatry Neurosci. 2006 Jul;31(4):229-45
pubmed: 16862241
J Comp Neurol. 1998 May 11;394(3):344-56
pubmed: 9579398
Brain Res Rev. 2007 Aug;55(1):144-54
pubmed: 17448541
J Comp Neurol. 1998 Dec 28;402(4):475-500
pubmed: 9862322
Neuropharmacology. 2021 Sep 15;196:108714
pubmed: 34271017
Pharmacol Rev. 2016 Jul;68(3):816-71
pubmed: 27363441
J Comp Neurol. 1996 Sep 09;373(1):76-89
pubmed: 8876464
Cell Rep. 2017 Aug 22;20(8):1881-1892
pubmed: 28834751
Cell. 2020 Jun 11;181(6):1364-1379.e14
pubmed: 32470395
Nature. 1981 Dec 10;294(5841):587-9
pubmed: 6273751
Front Endocrinol (Lausanne). 2013 Mar 22;4:36
pubmed: 23526754
Sci Signal. 2018 Jan 09;11(512):
pubmed: 29317519
Brain Res. 1985 Feb 18;327(1-2):385-9
pubmed: 2985182
Endocrinology. 2015 May;156(5):1692-700
pubmed: 25734363
Annu Rev Neurosci. 2016 Jul 8;39:257-76
pubmed: 27145911