HIV Transgenic Rats Demonstrate Impaired Sensorimotor Gating But Are Insensitive to Cannabinoid (Δ9-Tetrahydrocannabinol)-Induced Deficits.
Acoustic Stimulation
Animals
Cannabidiol
/ pharmacology
Cannabinoid Receptor Agonists
/ pharmacology
Cannabinoids
/ pharmacology
Dronabinol
/ pharmacology
Female
HIV Infections
/ physiopathology
Hallucinogens
/ pharmacology
Male
Prepulse Inhibition
/ drug effects
Rats
Rats, Transgenic
Reflex, Startle
/ drug effects
Sensory Gating
/ drug effects
CBD
HAND
HIV
PPI
THC
Journal
The international journal of neuropsychopharmacology
ISSN: 1469-5111
Titre abrégé: Int J Neuropsychopharmacol
Pays: England
ID NLM: 9815893
Informations de publication
Date de publication:
12 11 2021
12 11 2021
Historique:
received:
16
11
2020
revised:
24
05
2021
accepted:
30
07
2021
pubmed:
3
8
2021
medline:
3
2
2022
entrez:
2
8
2021
Statut:
ppublish
Résumé
HIV-associated neurocognitive disorder (HAND) is commonly observed in persons living with HIV (PWH) and is characterized by cognitive deficits implicating disruptions of fronto-striatal neurocircuitry. Such circuitry is also susceptible to alteration by cannabis and other drugs of abuse. PWH use cannabis at much higher rates than the general population, thus prioritizing the characterization of any interactions between HIV and cannabinoids on cognitively relevant systems. Prepulse inhibition (PPI) of the startle response, the process by which the motor response to a startling stimulus is attenuated by perception of a preceding non-startling stimulus, is an operational assay of fronto-striatal circuit integrity that is translatable across species. PPI is reduced in PWH. The HIV transgenic (HIVtg) rat model of HIV infection mimics numerous aspects of HAND, although to date the PPI deficit observed in PWH has yet to be fully recreated in animals. PPI was measured in male and female HIVtg rats and wild-type controls following acute, nonconcurrent treatment with the primary constituents of cannabis: Δ 9-tetrahydrocannabinol (THC; 1 and 3 mg/kg, s.c.) and cannabidiol (1, 10, and 30 mg/kg, i.p.). HIVtg rats exhibited a significant PPI deficit relative to wild-type controls. THC reduced PPI in controls but not HIVtg rats. Cannabidiol exerted only minor, genotype-independent effects on PPI. HIVtg rats exhibit a relative insensitivity to the deleterious effects of THC on the fronto-striatal function reflected by PPI, which may partially explain the higher rates of cannabis use among PWH.
Sections du résumé
BACKGROUND
HIV-associated neurocognitive disorder (HAND) is commonly observed in persons living with HIV (PWH) and is characterized by cognitive deficits implicating disruptions of fronto-striatal neurocircuitry. Such circuitry is also susceptible to alteration by cannabis and other drugs of abuse. PWH use cannabis at much higher rates than the general population, thus prioritizing the characterization of any interactions between HIV and cannabinoids on cognitively relevant systems. Prepulse inhibition (PPI) of the startle response, the process by which the motor response to a startling stimulus is attenuated by perception of a preceding non-startling stimulus, is an operational assay of fronto-striatal circuit integrity that is translatable across species. PPI is reduced in PWH. The HIV transgenic (HIVtg) rat model of HIV infection mimics numerous aspects of HAND, although to date the PPI deficit observed in PWH has yet to be fully recreated in animals.
METHODS
PPI was measured in male and female HIVtg rats and wild-type controls following acute, nonconcurrent treatment with the primary constituents of cannabis: Δ 9-tetrahydrocannabinol (THC; 1 and 3 mg/kg, s.c.) and cannabidiol (1, 10, and 30 mg/kg, i.p.).
RESULTS
HIVtg rats exhibited a significant PPI deficit relative to wild-type controls. THC reduced PPI in controls but not HIVtg rats. Cannabidiol exerted only minor, genotype-independent effects on PPI.
CONCLUSIONS
HIVtg rats exhibit a relative insensitivity to the deleterious effects of THC on the fronto-striatal function reflected by PPI, which may partially explain the higher rates of cannabis use among PWH.
Identifiants
pubmed: 34338765
pii: 6335362
doi: 10.1093/ijnp/pyab053
pmc: PMC8598295
doi:
Substances chimiques
Cannabinoid Receptor Agonists
0
Cannabinoids
0
Hallucinogens
0
Cannabidiol
19GBJ60SN5
Dronabinol
7J8897W37S
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
894-906Subventions
Organisme : NIDA NIH HHS
ID : P50 DA026306
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA043535
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA051295
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA044909
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of CINP.
Références
AIDS Educ Prev. 2018 Apr;30(2):169-181
pubmed: 29688777
Lancet Psychiatry. 2016 Oct;3(10):954-964
pubmed: 27592339
Neuroscience. 1984 Dec;13(4):1189-215
pubmed: 6152036
J Addict Dis. 1997;16(3):25-30
pubmed: 9243337
J Neuroimmune Pharmacol. 2013 Sep;8(4):988-97
pubmed: 23690140
Res Commun Chem Pathol Pharmacol. 1973 May;5(3):621-6
pubmed: 4701259
AIDS Behav. 2017 Apr;21(4):1138-1148
pubmed: 27738780
Am J Med Genet B Neuropsychiatr Genet. 2009 Jun 5;150B(4):545-53
pubmed: 18785205
J Psychopharmacol. 1992 Jan;6(2):176-90
pubmed: 22291349
J Acquir Immune Defic Syndr. 2005 Jan 1;38(1):43-6
pubmed: 15608523
Antiviral Res. 2010 Dec;88(3):334-42
pubmed: 20970459
J Neurovirol. 2011 Feb;17(1):3-16
pubmed: 21174240
Behav Brain Res. 2011 Sep 23;222(2):299-308
pubmed: 21458498
Front Neurosci. 2018 Oct 23;12:703
pubmed: 30405327
Neuropsychopharmacology. 2012 Apr;37(5):1216-23
pubmed: 22218093
J Psychopharmacol. 2016 Nov;30(11):1072-1081
pubmed: 27539931
Eur Neuropsychopharmacol. 2017 Dec;27(12):1223-1237
pubmed: 29129557
Front Pharmacol. 2014 Feb 06;5:10
pubmed: 24567721
J Int Neuropsychol Soc. 2013 Jul;19(6):709-17
pubmed: 23552464
Biol Psychiatry. 1993 Sep 15;34(6):361-72
pubmed: 8218603
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 2;106:110089
pubmed: 32891668
Br J Pharmacol. 2008 Jan;153(2):199-215
pubmed: 17828291
J Neurovirol. 2017 Feb;23(1):87-98
pubmed: 27538996
Behav Pharmacol. 2000 Jun;11(3-4):185-204
pubmed: 11103873
Psychopharmacology (Berl). 2006 Nov;188(4):425-44
pubmed: 17019571
Schizophr Res. 2007 Jan;89(1-3):225-31
pubmed: 17005374
J Neuroimmune Pharmacol. 2017 Mar;12(1):171-179
pubmed: 27699630
J Neuroimmune Pharmacol. 2020 Jun;15(2):264-279
pubmed: 31858373
J Psychopharmacol. 2017 Aug;31(8):1035-1045
pubmed: 28648138
Psychopharmacology (Berl). 2008 Aug;199(3):331-88
pubmed: 18568339
Int J Neuropsychopharmacol. 2010 Aug;13(7):861-76
pubmed: 19785914
J Neurovirol. 2018 Apr;24(2):229-245
pubmed: 28730408
Neuropsychopharmacology. 2006 Apr;31(4):795-803
pubmed: 16052245
J Parkinsons Dis. 2014;4(1):77-87
pubmed: 24366928
J Neuroimmunol. 2010 Jan 25;218(1-2):94-101
pubmed: 19913921
J Gen Intern Med. 2001 Sep;16(9):625-33
pubmed: 11556944
Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9271-6
pubmed: 11481487
PLoS One. 2017 Nov 27;12(11):e0188404
pubmed: 29176843
Front Pharmacol. 2018 Aug 21;9:901
pubmed: 30186164
Br J Pharmacol. 2005 Dec;146(7):913-5
pubmed: 16205721
Neuropsychopharmacology. 2015 May;40(6):1436-47
pubmed: 25510937
Behav Brain Res. 2006 Jan 6;166(1):101-9
pubmed: 16143410
Brain Res. 1992 Mar 20;575(2):341-6
pubmed: 1349255
Mol Neurobiol. 2019 May;56(5):3563-3575
pubmed: 30151725
Psychopharmacology (Berl). 2001 Jul;156(2-3):194-215
pubmed: 11549223
Clin Infect Dis. 2018 Jun 1;66(12):1872-1882
pubmed: 29471387
Synapse. 2018 Mar;72(3):
pubmed: 29178372
Arch Gen Psychiatry. 2006 Dec;63(12):1325-35
pubmed: 17146007
Pharmacol Biochem Behav. 2006 Jun;84(2):330-6
pubmed: 16820196
Eur Neuropsychopharmacol. 2014 Aug;24(8):1415-23
pubmed: 24846537
Psychopharmacology (Berl). 1988;94(4):507-14
pubmed: 3131796
Psychol Med. 2010 Mar;40(3):383-98
pubmed: 19627647
Psychol Med. 1995 Nov;25(6):1233-46
pubmed: 8637953
Neuropsychopharmacology. 2010 Feb;35(3):764-74
pubmed: 19924114
Synapse. 2006 Nov;60(6):429-36
pubmed: 16881072
AIDS Care. 2016;28(5):628-32
pubmed: 26694807
J Neurosci. 2001 Jan 1;21(1):109-16
pubmed: 11150326
Sci Rep. 2018 Jan 9;8(1):136
pubmed: 29317696
Neurology. 2010 Dec 7;75(23):2087-96
pubmed: 21135382
J Neurovirol. 2019 Oct;25(5):686-701
pubmed: 30607890
Int J Dev Neurosci. 2017 Apr;57:12-20
pubmed: 28040491
Int J Neuropsychopharmacol. 2014 Oct 31;18(5):
pubmed: 25618402
Drug Alcohol Depend. 2017 Jan 01;170:120-127
pubmed: 27889592
Eur J Pharmacol. 2001 Oct 26;430(1):41-7
pubmed: 11698061
Arch Intern Med. 1998 Nov 9;158(20):2257-64
pubmed: 9818806
J Neurosci. 2019 Oct 30;39(44):8762-8777
pubmed: 31570536
Curr HIV Res. 2012 Jul;10(5):415-24
pubmed: 22591365
Psychiatry Res Neuroimaging. 2018 Jun 8;278:21-34
pubmed: 29957349
J Neurosci. 1991 Feb;11(2):563-83
pubmed: 1992016
Sci Rep. 2016 Sep 06;6:32831
pubmed: 27596023
AIDS Behav. 2020 Apr;24(4):1275-1280
pubmed: 30778810
Philos Trans R Soc Lond B Biol Sci. 1971 Sep 30;262(845):383-401
pubmed: 4107495
Brain Res. 1996 May 25;722(1-2):168-76
pubmed: 8813362
Psychopharmacology (Berl). 1990;102(2):156-62
pubmed: 2177204
Front Behav Neurosci. 2018 Nov 22;12:285
pubmed: 30524255
Curr Drug Abuse Rev. 2017;9(2):126-141
pubmed: 27138170
Brain Behav Immun. 2015 Aug;48:336-49
pubmed: 25733103
Brain Res. 2003 Jul 25;979(1-2):235-9
pubmed: 12850592
Exp Neurol. 2013 Jan;239:139-47
pubmed: 23063600
Science. 1997 Jun 27;276(5321):2048-50
pubmed: 9197269
J Addict Med. 2011 Mar;5(1):1-8
pubmed: 21321675
eNeuro. 2020 Jun 19;7(3):
pubmed: 32471847
Psychopharmacology (Berl). 2008 Jun;198(3):375-85
pubmed: 18446326
Am J Epidemiol. 2013 Jan 15;177(2):116-25
pubmed: 23287403
J Pharmacol Exp Ther. 1989 Oct;251(1):378-87
pubmed: 2552079
J Int Neuropsychol Soc. 2007 May;13(3):549-54
pubmed: 17445305
J Neuroimmune Pharmacol. 2014 Dec;9(5):642-53
pubmed: 25037595