Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice

Kunlin Jin, Lin Xie, Sun Hee Kim, Sophie Parmentier-Batteur, Yunjuan Sun, Xiao Ou Mao, Jocelyn Childs, David A. Greenberg

Research output: Contribution to journalArticle

206 Citations (Scopus)

Abstract

Pharmacological studies suggest a role for CB1 cannabinoid receptors (CB1R) in regulating neurogenesis in the adult brain. To investigate this possibility, we measured neurogenesis by intraperitoneal injection of bromodeoxyuridine (BrdU), which labels newborn neurons, in wild-type and CB1R-knockout (CB1R-KO) mice. CB1R-KO mice showed reductions in the number of BrdU-labeled cells to ∼50% of wild-type (WT) levels in dentate gyrus and subventricular zone (SVZ), suggesting that CB1R activation promotes neurogenesis. To test this further, WT mice were given the CB1R antagonist N-(piperidin-1-yl)-5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716A) before measuring neurogenesis with BrdU. SR141716A paradoxically increased the number of BrdU-labeled cells by ∼50% in SVZ; another CB1R antagonist, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1- piperidinyl-1H-pyrazole-3-carboxamide (AM251), had a similar effect. To investigate this discrepancy, SR141716A was given to CB1R-KO mice, in which it still stimulated neurogenesis, indicating involvement of a non-CB1 receptor. Action at one such non-CB1, SR141716A-sensitive site, the VR1 vanilloid receptor, was tested by administering SR141716A to VR1-KO mice, in which the ability of SR141716A to enhance neurogenesis was abolished. Thus, CB1 and VR1 receptors both seem to have roles in regulating adult neurogenesis.

Original languageEnglish
Pages (from-to)204-208
Number of pages5
JournalMolecular Pharmacology
Volume66
Issue number2
DOIs
StatePublished - 1 Aug 2004

Fingerprint

rimonabant
Cannabinoid Receptor CB1
Neurogenesis
Knockout Mice
Bromodeoxyuridine
Cannabinoid Receptor Antagonists
Lateral Ventricles
Dentate Gyrus
Intraperitoneal Injections

Cite this

Jin, K., Xie, L., Kim, S. H., Parmentier-Batteur, S., Sun, Y., Mao, X. O., ... Greenberg, D. A. (2004). Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice. Molecular Pharmacology, 66(2), 204-208. https://doi.org/10.1124/mol.66.2.204
Jin, Kunlin ; Xie, Lin ; Kim, Sun Hee ; Parmentier-Batteur, Sophie ; Sun, Yunjuan ; Mao, Xiao Ou ; Childs, Jocelyn ; Greenberg, David A. / Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice. In: Molecular Pharmacology. 2004 ; Vol. 66, No. 2. pp. 204-208.
@article{992ad9a342df441d9f7e76fa05d6d371,
title = "Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice",
abstract = "Pharmacological studies suggest a role for CB1 cannabinoid receptors (CB1R) in regulating neurogenesis in the adult brain. To investigate this possibility, we measured neurogenesis by intraperitoneal injection of bromodeoxyuridine (BrdU), which labels newborn neurons, in wild-type and CB1R-knockout (CB1R-KO) mice. CB1R-KO mice showed reductions in the number of BrdU-labeled cells to ∼50{\%} of wild-type (WT) levels in dentate gyrus and subventricular zone (SVZ), suggesting that CB1R activation promotes neurogenesis. To test this further, WT mice were given the CB1R antagonist N-(piperidin-1-yl)-5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716A) before measuring neurogenesis with BrdU. SR141716A paradoxically increased the number of BrdU-labeled cells by ∼50{\%} in SVZ; another CB1R antagonist, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1- piperidinyl-1H-pyrazole-3-carboxamide (AM251), had a similar effect. To investigate this discrepancy, SR141716A was given to CB1R-KO mice, in which it still stimulated neurogenesis, indicating involvement of a non-CB1 receptor. Action at one such non-CB1, SR141716A-sensitive site, the VR1 vanilloid receptor, was tested by administering SR141716A to VR1-KO mice, in which the ability of SR141716A to enhance neurogenesis was abolished. Thus, CB1 and VR1 receptors both seem to have roles in regulating adult neurogenesis.",
author = "Kunlin Jin and Lin Xie and Kim, {Sun Hee} and Sophie Parmentier-Batteur and Yunjuan Sun and Mao, {Xiao Ou} and Jocelyn Childs and Greenberg, {David A.}",
year = "2004",
month = "8",
day = "1",
doi = "10.1124/mol.66.2.204",
language = "English",
volume = "66",
pages = "204--208",
journal = "Molecular Pharmacology",
issn = "0026-895X",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

Jin, K, Xie, L, Kim, SH, Parmentier-Batteur, S, Sun, Y, Mao, XO, Childs, J & Greenberg, DA 2004, 'Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice', Molecular Pharmacology, vol. 66, no. 2, pp. 204-208. https://doi.org/10.1124/mol.66.2.204

Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice. / Jin, Kunlin; Xie, Lin; Kim, Sun Hee; Parmentier-Batteur, Sophie; Sun, Yunjuan; Mao, Xiao Ou; Childs, Jocelyn; Greenberg, David A.

In: Molecular Pharmacology, Vol. 66, No. 2, 01.08.2004, p. 204-208.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice

AU - Jin, Kunlin

AU - Xie, Lin

AU - Kim, Sun Hee

AU - Parmentier-Batteur, Sophie

AU - Sun, Yunjuan

AU - Mao, Xiao Ou

AU - Childs, Jocelyn

AU - Greenberg, David A.

PY - 2004/8/1

Y1 - 2004/8/1

N2 - Pharmacological studies suggest a role for CB1 cannabinoid receptors (CB1R) in regulating neurogenesis in the adult brain. To investigate this possibility, we measured neurogenesis by intraperitoneal injection of bromodeoxyuridine (BrdU), which labels newborn neurons, in wild-type and CB1R-knockout (CB1R-KO) mice. CB1R-KO mice showed reductions in the number of BrdU-labeled cells to ∼50% of wild-type (WT) levels in dentate gyrus and subventricular zone (SVZ), suggesting that CB1R activation promotes neurogenesis. To test this further, WT mice were given the CB1R antagonist N-(piperidin-1-yl)-5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716A) before measuring neurogenesis with BrdU. SR141716A paradoxically increased the number of BrdU-labeled cells by ∼50% in SVZ; another CB1R antagonist, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1- piperidinyl-1H-pyrazole-3-carboxamide (AM251), had a similar effect. To investigate this discrepancy, SR141716A was given to CB1R-KO mice, in which it still stimulated neurogenesis, indicating involvement of a non-CB1 receptor. Action at one such non-CB1, SR141716A-sensitive site, the VR1 vanilloid receptor, was tested by administering SR141716A to VR1-KO mice, in which the ability of SR141716A to enhance neurogenesis was abolished. Thus, CB1 and VR1 receptors both seem to have roles in regulating adult neurogenesis.

AB - Pharmacological studies suggest a role for CB1 cannabinoid receptors (CB1R) in regulating neurogenesis in the adult brain. To investigate this possibility, we measured neurogenesis by intraperitoneal injection of bromodeoxyuridine (BrdU), which labels newborn neurons, in wild-type and CB1R-knockout (CB1R-KO) mice. CB1R-KO mice showed reductions in the number of BrdU-labeled cells to ∼50% of wild-type (WT) levels in dentate gyrus and subventricular zone (SVZ), suggesting that CB1R activation promotes neurogenesis. To test this further, WT mice were given the CB1R antagonist N-(piperidin-1-yl)-5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716A) before measuring neurogenesis with BrdU. SR141716A paradoxically increased the number of BrdU-labeled cells by ∼50% in SVZ; another CB1R antagonist, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1- piperidinyl-1H-pyrazole-3-carboxamide (AM251), had a similar effect. To investigate this discrepancy, SR141716A was given to CB1R-KO mice, in which it still stimulated neurogenesis, indicating involvement of a non-CB1 receptor. Action at one such non-CB1, SR141716A-sensitive site, the VR1 vanilloid receptor, was tested by administering SR141716A to VR1-KO mice, in which the ability of SR141716A to enhance neurogenesis was abolished. Thus, CB1 and VR1 receptors both seem to have roles in regulating adult neurogenesis.

UR - http://www.scopus.com/inward/record.url?scp=3342979420&partnerID=8YFLogxK

U2 - 10.1124/mol.66.2.204

DO - 10.1124/mol.66.2.204

M3 - Article

C2 - 15266010

AN - SCOPUS:3342979420

VL - 66

SP - 204

EP - 208

JO - Molecular Pharmacology

JF - Molecular Pharmacology

SN - 0026-895X

IS - 2

ER -

Jin K, Xie L, Kim SH, Parmentier-Batteur S, Sun Y, Mao XO et al. Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice. Molecular Pharmacology. 2004 Aug 1;66(2):204-208. https://doi.org/10.1124/mol.66.2.204