The role of NMDA receptors in rat propofol self-administration.
MK-801
NMDA receptor
Propofol
Reinforcement
Self-administration
Journal
BMC anesthesiology
ISSN: 1471-2253
Titre abrégé: BMC Anesthesiol
Pays: England
ID NLM: 100968535
Informations de publication
Date de publication:
15 06 2020
15 06 2020
Historique:
received:
31
01
2020
accepted:
26
05
2020
entrez:
17
6
2020
pubmed:
17
6
2020
medline:
10
8
2021
Statut:
epublish
Résumé
Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators neural plasticity, neuronal development, addiction, and neurodegeneration. In the present study, we explored the role of these receptors in the context of rat propofol self-administration. Sprague-Dawley Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using a fixed-ratio (FR) schedule over the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, followed 10 min later by a propofol self-administration session. After training, rats successfully underwent acquisition of propofol self-administration, as evidenced by a significant and stable rise in the number of active nose-pokes resulting in propofol administration relative to the number of control inactive nose-pokes (P < 0.01). As compared to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited a significantly greater number of propofol infusions (F (3, 28) = 4.372, P < 0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg of this compound. In addition, MK-801 failed to alter the numbers of active (F (3, 28) = 1.353, P > 0.05) or inactive (F (3, 28) = 0.047, P > 0.05) responses in these study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg MK-801 (P = 0.006, P < 0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group displayed a significant reduction in the number of active nose-poke responses (F (3, 20) = 20.8673, P < 0.01) and the number of sucrose pellets (F (3, 20) = 23.77, P < 0.01), while their locomotor activity was increased (F (3, 20) = 22.812, P < 0.01). These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.
Sections du résumé
BACKGROUND
Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators neural plasticity, neuronal development, addiction, and neurodegeneration. In the present study, we explored the role of these receptors in the context of rat propofol self-administration.
METHODS
Sprague-Dawley Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using a fixed-ratio (FR) schedule over the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, followed 10 min later by a propofol self-administration session.
RESULTS
After training, rats successfully underwent acquisition of propofol self-administration, as evidenced by a significant and stable rise in the number of active nose-pokes resulting in propofol administration relative to the number of control inactive nose-pokes (P < 0.01). As compared to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited a significantly greater number of propofol infusions (F (3, 28) = 4.372, P < 0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg of this compound. In addition, MK-801 failed to alter the numbers of active (F (3, 28) = 1.353, P > 0.05) or inactive (F (3, 28) = 0.047, P > 0.05) responses in these study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg MK-801 (P = 0.006, P < 0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group displayed a significant reduction in the number of active nose-poke responses (F (3, 20) = 20.8673, P < 0.01) and the number of sucrose pellets (F (3, 20) = 23.77, P < 0.01), while their locomotor activity was increased (F (3, 20) = 22.812, P < 0.01).
CONCLUSION
These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.
Identifiants
pubmed: 32539742
doi: 10.1186/s12871-020-01056-0
pii: 10.1186/s12871-020-01056-0
pmc: PMC7294660
doi:
Substances chimiques
Receptors, N-Methyl-D-Aspartate
0
Sucrose
57-50-1
Dizocilpine Maleate
6LR8C1B66Q
Propofol
YI7VU623SF
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
149Subventions
Organisme : NSFC
ID : 81271469
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81771431
Pays : International
Références
Curr Opin Pharmacol. 2009 Feb;9(1):59-64
pubmed: 19157986
Neuroscience. 2007 Feb 23;144(4):1209-18
pubmed: 17184925
Neuroreport. 2018 Mar 21;29(5):347-352
pubmed: 29369902
Neuroscience. 2013 Feb 12;231:373-83
pubmed: 23201252
J Neurophysiol. 1998 Jan;79(1):240-52
pubmed: 9425195
Psychopharmacology (Berl). 1996 Nov;128(1):83-8
pubmed: 8944410
Biol Psychiatry. 2012 Jun 1;71(11):1015-21
pubmed: 21907974
Br J Anaesth. 1996 Sep;77(3):385-6
pubmed: 8949816
Learn Mem. 2008 Dec 02;15(12):857-65
pubmed: 19050157
Trends Pharmacol Sci. 1992 May;13(5):177-84
pubmed: 1604710
Postgrad Med J. 1985;61 Suppl 3:133-7
pubmed: 3877281
Prog Neurobiol. 2001 Feb;63(3):241-320
pubmed: 11115727
Neurochem Res. 1991 Apr;16(4):443-6
pubmed: 1681436
Neuropharmacology. 1995 May;34(5):533-40
pubmed: 7566488
Science. 1991 Jan 4;251(4989):85-7
pubmed: 1824728
J Pharmacol Exp Ther. 1993 Oct;267(1):486-95
pubmed: 8229779
Neurosci Bull. 2016 Dec;32(6):531-537
pubmed: 27783327
Anesthesiology. 1992 Oct;77(4):817-8
pubmed: 1416179
Mol Neurobiol. 2001 Apr-Jun;23(2-3):83-99
pubmed: 11817219
Behav Pharmacol. 2014 Feb;25(1):80-91
pubmed: 24370559
Behav Pharmacol. 2006 Jun;17(4):295-302
pubmed: 16914947
Psychopharmacology (Berl). 1990;101(3):317-23
pubmed: 2163537
Eur J Neurosci. 1998 Apr;10(4):1241-51
pubmed: 9749778
Brain Res Bull. 1996;40(3):201-7
pubmed: 8736582
Behav Pharmacol. 1993 Dec;4(6):652-659
pubmed: 11224234
Eur J Pharmacol. 1996 Aug 1;309(1):1-11
pubmed: 8864686
Psychopharmacology (Berl). 1997 Sep;133(2):188-95
pubmed: 9342786
Br J Anaesth. 1984 Oct;56(10):1143-51
pubmed: 6332639
Brain Res. 2008 Dec 3;1243:1-9
pubmed: 18822274
Pharmacol Ther. 2003 Sep;99(3):311-26
pubmed: 12951163
Life Sci. 1992;50(21):PL167-72
pubmed: 1533700
Anesthesiology. 1997 Oct;87(4):935-43
pubmed: 9357897
Psychopharmacology (Berl). 2014 Jul;231(13):2705-16
pubmed: 24522331
Br J Pharmacol. 1995 Sep;116(2):1761-8
pubmed: 8528557
Psychopharmacology (Berl). 2000 Dec;153(1):148-54
pubmed: 11255925
Oxid Med Cell Longev. 2010 Jan-Feb;3(1):13-22
pubmed: 20716924
Trends Neurosci. 1999 Nov;22(11):521-7
pubmed: 10529820
Anesthesiology. 1996 Jul;85(1):121-8
pubmed: 8694357