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
Y1 - 2004/8
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
SN - 0026-895X
VL - 66
SP - 204
EP - 208
JO - Molecular Pharmacology
JF - Molecular Pharmacology
IS - 2
ER -