TY - JOUR
T1 - Species and strain differences in the expression of a novel glutamate-modulating cannabinoid receptor in the rodent hippocampus
AU - Hoffman, Alexander F.
AU - Macgill, Alice M.
AU - Smith, Dennison
AU - Oz, Murat
AU - Lupica, Carl R.
PY - 2005/11
Y1 - 2005/11
N2 - A novel, non-CB1 cannabinoid receptor has been defined by the persistence of inhibition of glutamatergic EPSPs by the cannabinoid receptor agonist WIN55,212-2 in mice lacking the cloned CB1 receptor (CBr-/-) (Hajos et al., 2001). This novel receptor was also distinguished from CB1 by its sensitivity to the antagonist SR141716A and its insensitivity to the antagonist AM251 (Hajos & Freund, 2002). We have chosen to refer to this putative receptor as CBsc due to its identification on Schaffer collateral axon terminals in the hippocampus. We examined properties of CBsc receptors in Sprague Dawley (SD) rats and two strains of wild-type (WT) mice (C57BL/6J and CD1) used as backgrounds for two independent lines of CB1-/- mice (Ledent et al., 1999; Zimmer et al., 1999). The inhibition of synaptic glutamate release by WIN55,212-2 was observed in hippocampal slices from WT CD1 mice and SD rats but was absent in WT C57 mice. We also found that AM251 and SR141716A antagonized the effect of WIN55,212-2 in hippocampal slices from CD1 mice and SD rats demonstrating a lack of selectivity of these ligands for CB1 and CBsc receptors in these animals. The results indicate that the glutamate-modulating CBsc cannabinoid receptor is present in the hippocampi of CD1 mice and SD rats but not in C57BL/6J mice. Thus, we have identified animal models that may permit the study of cannabinoids independently of the novel CBsc receptor (C57 CB1+/+), the CBsc receptor independently of the cloned CB1 receptor (CDICB1-/-), or in the absence of both receptors (C57 CB1-/-).
AB - A novel, non-CB1 cannabinoid receptor has been defined by the persistence of inhibition of glutamatergic EPSPs by the cannabinoid receptor agonist WIN55,212-2 in mice lacking the cloned CB1 receptor (CBr-/-) (Hajos et al., 2001). This novel receptor was also distinguished from CB1 by its sensitivity to the antagonist SR141716A and its insensitivity to the antagonist AM251 (Hajos & Freund, 2002). We have chosen to refer to this putative receptor as CBsc due to its identification on Schaffer collateral axon terminals in the hippocampus. We examined properties of CBsc receptors in Sprague Dawley (SD) rats and two strains of wild-type (WT) mice (C57BL/6J and CD1) used as backgrounds for two independent lines of CB1-/- mice (Ledent et al., 1999; Zimmer et al., 1999). The inhibition of synaptic glutamate release by WIN55,212-2 was observed in hippocampal slices from WT CD1 mice and SD rats but was absent in WT C57 mice. We also found that AM251 and SR141716A antagonized the effect of WIN55,212-2 in hippocampal slices from CD1 mice and SD rats demonstrating a lack of selectivity of these ligands for CB1 and CBsc receptors in these animals. The results indicate that the glutamate-modulating CBsc cannabinoid receptor is present in the hippocampi of CD1 mice and SD rats but not in C57BL/6J mice. Thus, we have identified animal models that may permit the study of cannabinoids independently of the novel CBsc receptor (C57 CB1+/+), the CBsc receptor independently of the cloned CB1 receptor (CDICB1-/-), or in the absence of both receptors (C57 CB1-/-).
KW - C57BL mouse
KW - CB1 cannabinoid receptor
KW - CD1 mouse
KW - Electrophysiology
KW - Knockout
KW - Sprague Dawley rat
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U2 - 10.1111/j.1460-9568.2005.04401.x
DO - 10.1111/j.1460-9568.2005.04401.x
M3 - Article
C2 - 16262678
AN - SCOPUS:27844492824
SN - 0953-816X
VL - 22
SP - 2387
EP - 2391
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 9
ER -