Activation-dependent subcellular distribution patterns of CB1 Cannabinoid Receptors in the Rat Forebrain

Karine Thibault, Damien Carrel, Damien Bonnard, Katalin Gallatz, Anne Simon, Marc Biard, Sophie Pezet, M. Palkóvits, Zsolt Lenkei

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Chronic cannabinoid exposure results in tolerance due to region-specific desensitization and down-regulation of CB1 cannabinoid receptors (CB1Rs). For most G-protein-coupled receptors, internalization closely follows rapid desensitization as an important component of long-term down-regulation. However, in vivo patterns of CB1R internalization are not known. Here we investigate the subcellular redistribution of CB1Rs in the rat forebrain following activation by agonist CP55 940 or inhibition by antagonist/inverse agonist AM251. At steady state, CB1Rs are mainly localized to the cell membrane of preterminal axon shafts and, to a lesser degree, to synaptic terminals. A high proportion of CB1Rs is also localized to somatodendritic endosomes. Inhibition of basal activation by acute AM251 administration decreases the number of cell bodies containing CB1R-immunoreactive endosomes, suggesting that CB1Rs are permanently activated and internalized at steady state. On the contrary, acute agonist treatment induces rapid and important increase of endosomal CB1R immunolabeling, likely due to internalization and retrograde transport of axonal CB1Rs. Repeated agonist treatment is necessary to significantly reduce initially high levels of axonal CB1R labeling, in addition to increasing somatodendritic endosomal CB1R labeling in cholecystokinin-positive interneurons. This redistribution displays important region-specific differences; it is most pronounced in the neocortex and hippocampus and absent in basal ganglia.

Original languageEnglish
Pages (from-to)2581-2591
Number of pages11
JournalCerebral Cortex
Volume23
Issue number11
DOIs
Publication statusPublished - Nov 2013

Fingerprint

Cannabinoid Receptor CB1
Prosencephalon
Endosomes
Down-Regulation
Axonal Transport
Cannabinoids
Neocortex
Cholecystokinin
Presynaptic Terminals
Interneurons
G-Protein-Coupled Receptors
Basal Ganglia
Axons
Hippocampus
Cell Membrane

Keywords

  • axon
  • basal ganglia
  • endocytosis
  • redistribution
  • tolerance

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Thibault, K., Carrel, D., Bonnard, D., Gallatz, K., Simon, A., Biard, M., ... Lenkei, Z. (2013). Activation-dependent subcellular distribution patterns of CB1 Cannabinoid Receptors in the Rat Forebrain. Cerebral Cortex, 23(11), 2581-2591. https://doi.org/10.1093/cercor/bhs240

Activation-dependent subcellular distribution patterns of CB1 Cannabinoid Receptors in the Rat Forebrain. / Thibault, Karine; Carrel, Damien; Bonnard, Damien; Gallatz, Katalin; Simon, Anne; Biard, Marc; Pezet, Sophie; Palkóvits, M.; Lenkei, Zsolt.

In: Cerebral Cortex, Vol. 23, No. 11, 11.2013, p. 2581-2591.

Research output: Contribution to journalArticle

Thibault, K, Carrel, D, Bonnard, D, Gallatz, K, Simon, A, Biard, M, Pezet, S, Palkóvits, M & Lenkei, Z 2013, 'Activation-dependent subcellular distribution patterns of CB1 Cannabinoid Receptors in the Rat Forebrain', Cerebral Cortex, vol. 23, no. 11, pp. 2581-2591. https://doi.org/10.1093/cercor/bhs240
Thibault, Karine ; Carrel, Damien ; Bonnard, Damien ; Gallatz, Katalin ; Simon, Anne ; Biard, Marc ; Pezet, Sophie ; Palkóvits, M. ; Lenkei, Zsolt. / Activation-dependent subcellular distribution patterns of CB1 Cannabinoid Receptors in the Rat Forebrain. In: Cerebral Cortex. 2013 ; Vol. 23, No. 11. pp. 2581-2591.
@article{e786e7d65c5649439b9c4160e488f5f3,
title = "Activation-dependent subcellular distribution patterns of CB1 Cannabinoid Receptors in the Rat Forebrain",
abstract = "Chronic cannabinoid exposure results in tolerance due to region-specific desensitization and down-regulation of CB1 cannabinoid receptors (CB1Rs). For most G-protein-coupled receptors, internalization closely follows rapid desensitization as an important component of long-term down-regulation. However, in vivo patterns of CB1R internalization are not known. Here we investigate the subcellular redistribution of CB1Rs in the rat forebrain following activation by agonist CP55 940 or inhibition by antagonist/inverse agonist AM251. At steady state, CB1Rs are mainly localized to the cell membrane of preterminal axon shafts and, to a lesser degree, to synaptic terminals. A high proportion of CB1Rs is also localized to somatodendritic endosomes. Inhibition of basal activation by acute AM251 administration decreases the number of cell bodies containing CB1R-immunoreactive endosomes, suggesting that CB1Rs are permanently activated and internalized at steady state. On the contrary, acute agonist treatment induces rapid and important increase of endosomal CB1R immunolabeling, likely due to internalization and retrograde transport of axonal CB1Rs. Repeated agonist treatment is necessary to significantly reduce initially high levels of axonal CB1R labeling, in addition to increasing somatodendritic endosomal CB1R labeling in cholecystokinin-positive interneurons. This redistribution displays important region-specific differences; it is most pronounced in the neocortex and hippocampus and absent in basal ganglia.",
keywords = "axon, basal ganglia, endocytosis, redistribution, tolerance",
author = "Karine Thibault and Damien Carrel and Damien Bonnard and Katalin Gallatz and Anne Simon and Marc Biard and Sophie Pezet and M. Palk{\'o}vits and Zsolt Lenkei",
year = "2013",
month = "11",
doi = "10.1093/cercor/bhs240",
language = "English",
volume = "23",
pages = "2581--2591",
journal = "Cerebral Cortex",
issn = "1047-3211",
publisher = "Oxford University Press",
number = "11",

}

TY - JOUR

T1 - Activation-dependent subcellular distribution patterns of CB1 Cannabinoid Receptors in the Rat Forebrain

AU - Thibault, Karine

AU - Carrel, Damien

AU - Bonnard, Damien

AU - Gallatz, Katalin

AU - Simon, Anne

AU - Biard, Marc

AU - Pezet, Sophie

AU - Palkóvits, M.

AU - Lenkei, Zsolt

PY - 2013/11

Y1 - 2013/11

N2 - Chronic cannabinoid exposure results in tolerance due to region-specific desensitization and down-regulation of CB1 cannabinoid receptors (CB1Rs). For most G-protein-coupled receptors, internalization closely follows rapid desensitization as an important component of long-term down-regulation. However, in vivo patterns of CB1R internalization are not known. Here we investigate the subcellular redistribution of CB1Rs in the rat forebrain following activation by agonist CP55 940 or inhibition by antagonist/inverse agonist AM251. At steady state, CB1Rs are mainly localized to the cell membrane of preterminal axon shafts and, to a lesser degree, to synaptic terminals. A high proportion of CB1Rs is also localized to somatodendritic endosomes. Inhibition of basal activation by acute AM251 administration decreases the number of cell bodies containing CB1R-immunoreactive endosomes, suggesting that CB1Rs are permanently activated and internalized at steady state. On the contrary, acute agonist treatment induces rapid and important increase of endosomal CB1R immunolabeling, likely due to internalization and retrograde transport of axonal CB1Rs. Repeated agonist treatment is necessary to significantly reduce initially high levels of axonal CB1R labeling, in addition to increasing somatodendritic endosomal CB1R labeling in cholecystokinin-positive interneurons. This redistribution displays important region-specific differences; it is most pronounced in the neocortex and hippocampus and absent in basal ganglia.

AB - Chronic cannabinoid exposure results in tolerance due to region-specific desensitization and down-regulation of CB1 cannabinoid receptors (CB1Rs). For most G-protein-coupled receptors, internalization closely follows rapid desensitization as an important component of long-term down-regulation. However, in vivo patterns of CB1R internalization are not known. Here we investigate the subcellular redistribution of CB1Rs in the rat forebrain following activation by agonist CP55 940 or inhibition by antagonist/inverse agonist AM251. At steady state, CB1Rs are mainly localized to the cell membrane of preterminal axon shafts and, to a lesser degree, to synaptic terminals. A high proportion of CB1Rs is also localized to somatodendritic endosomes. Inhibition of basal activation by acute AM251 administration decreases the number of cell bodies containing CB1R-immunoreactive endosomes, suggesting that CB1Rs are permanently activated and internalized at steady state. On the contrary, acute agonist treatment induces rapid and important increase of endosomal CB1R immunolabeling, likely due to internalization and retrograde transport of axonal CB1Rs. Repeated agonist treatment is necessary to significantly reduce initially high levels of axonal CB1R labeling, in addition to increasing somatodendritic endosomal CB1R labeling in cholecystokinin-positive interneurons. This redistribution displays important region-specific differences; it is most pronounced in the neocortex and hippocampus and absent in basal ganglia.

KW - axon

KW - basal ganglia

KW - endocytosis

KW - redistribution

KW - tolerance

UR - http://www.scopus.com/inward/record.url?scp=84881566260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881566260&partnerID=8YFLogxK

U2 - 10.1093/cercor/bhs240

DO - 10.1093/cercor/bhs240

M3 - Article

C2 - 22892424

AN - SCOPUS:84881566260

VL - 23

SP - 2581

EP - 2591

JO - Cerebral Cortex

JF - Cerebral Cortex

SN - 1047-3211

IS - 11

ER -