Expression of the mRNA coding the cannabinoid receptor 2 in the pallidal complex of <i>Macaca fascicularis</i>

Lanciego, José L.; Barroso‐Chinea, Pedro; Rico, Alberto J.; Conte-Perales, Lorena; Callén, Lucía; Roda, Elvira; Gómez-Bautista, Virginia; López, Icíar P.; Lluı́s, Carmen; Labandeira-Garcı́a, José Luis; Franco, Rafael

doi:10.1177/0269881110367732

Cited by 127 publications

(99 citation statements)

References 42 publications

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“…Involvement of CB 2 receptors in the effect of WIN55212-2 in these experiments is unlikely, because the density of CB 2 receptors is generally very low in the brain, and CB 2 receptors are mostly localized on microglial cells and astrocytes (Munro et al, 1993;Fernandez-Ruiz et al, 2007). However, it must be noted that neuronal CB 2 receptors at low densities were observed in some brain regions recently (van Sickle et al, 2005;Gong et al, 2006;Brusco et al, 2008;Suarez et al, 2008;Lanciego et al, 2011).…”

Section: Discussionmentioning

confidence: 82%

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Kovacs

Knop

Urbanski

et al. 2011

Neuropsychopharmacol

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Activation of CB 1 receptors on axon terminals by exogenous cannabinoids (eg, D 9 -tetrahydrocannabinol) and by endogenous cannabinoids (endocannabinoids) released by postsynaptic neurons leads to presynaptic inhibition of neurotransmission. The aim of this study was to characterize the effect of cannabinoids on GABAergic synaptic transmission in the human neocortex. Brain slices were prepared from neocortical tissues surgically removed to eliminate epileptogenic foci. Spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) were recorded in putative pyramidal neurons using patch-clamp techniques. To enhance the activity of cannabinoidsensitive presynaptic axons, muscarinic receptors were continuously stimulated by carbachol. The synthetic cannabinoid receptor agonist WIN55212-2 decreased the cumulative amplitude of sIPSCs. The CB 1 antagonist rimonabant prevented this effect, verifying the involvement of CB 1 receptors. WIN55212-2 decreased the frequency of miniature IPSCs (mIPSCs) recorded in the presence of tetrodotoxin, but did not change their amplitude, indicating that the neurotransmission was inhibited presynaptically. Depolarization of postsynaptic pyramidal neurons induced a suppression of sIPSCs. As rimonabant prevented this suppression, it is very likely that it was due to endocannabinods acting on CB 1 receptors. This is the first demonstration that an exogenous cannabinoid inhibits synaptic transmission in the human neocortex and that endocannabinoids released by postsynaptic neurons suppress synaptic transmission in the human brain. Interferences of cannabinoid agonists and antagonists with synaptic transmission in the cortex may explain the cognitive and memory deficits elicited by these drugs.

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Section: Discussionmentioning

confidence: 82%

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Kovacs

Knop

Urbanski

et al. 2011

Neuropsychopharmacol

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“…In contrast, other studies using ISH and radioligand binding assays detected CB 2 mRNA and receptor binding in rat retina (7), mouse cerebral cortex (8), and hippocampus and striatum of nonhuman primates (9). More recent studies using RT-PCR also detected CB 2 mRNA in the cortex, striatum, hippocampus, amygdala, and brainstem (9)(10)(11)(12)(13)(14).…”

mentioning

confidence: 87%

“…More recent studies using RT-PCR also detected CB 2 mRNA in the cortex, striatum, hippocampus, amygdala, and brainstem (9)(10)(11)(12)(13)(14). Immunoblot and immunohistochemistry (IHC) assays detected CB 2 R immunoreactivity or immunostaining in various brain regions (13,(15)(16)(17)(18)(19)(20).…”

mentioning

confidence: 94%

Cannabinoid CB ₂ receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice

Zhang

Gao

Liu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

310

353

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Cannabinoid CB 2 receptors (CB 2 Rs) have been recently reported to modulate brain dopamine (DA)-related behaviors; however, the cellular mechanisms underlying these actions are unclear. Here we report that CB 2 Rs are expressed in ventral tegmental area (VTA) DA neurons and functionally modulate DA neuronal excitability and DA-related behavior. In situ hybridization and immunohistochemical assays detected CB 2 mRNA and CB 2 R immunostaining in VTA DA neurons. Electrophysiological studies demonstrated that activation of CB 2 Rs by JWH133 or other CB 2 R agonists inhibited VTA DA neuronal firing in vivo and ex vivo, whereas microinjections of JWH133 into the VTA inhibited cocaine self-administration. Importantly, all of the above findings observed in WT or CB 1 −/− mice are blocked by CB 2 R antagonist and absent in CB 2 −/− mice. These data suggest that CB 2 R-mediated reduction of VTA DA neuronal activity may underlie JWH133's modulation of DA-regulated behaviors.T he presence of functional cannabinoid CB 2 receptors (CB 2 Rs) in the brain has been controversial. When CB 2 Rs were first cloned, in situ hybridization (ISH) failed to detect CB 2 mRNA in brain (1). Similarly, Northern blot and polymerase chain reaction (PCR) assays failed to detect CB 2 mRNA in brain (2-5). Therefore, CB 2 Rs were considered "peripheral cannabinoid receptors" (1, 6).In contrast, other studies using ISH and radioligand binding assays detected CB 2 mRNA and receptor binding in rat retina (7), mouse cerebral cortex (8), and hippocampus and striatum of nonhuman primates (9). More recent studies using RT-PCR also detected CB 2 mRNA in the cortex, striatum, hippocampus, amygdala, and brainstem (9-14). Immunoblot and immunohistochemistry (IHC) assays detected CB 2 R immunoreactivity or immunostaining in various brain regions (13,(15)(16)(17)(18)(19)(20). The specificities of the detected CB 2 R protein and CB 2 -mRNA remain questionable, however, owing to a lack of controls using CB 1 −/− and CB 2 −/− mice in most previous studies (21). A currently accepted view is that brain CB 2 Rs are expressed predominantly in activated microglia during neuroinflammation, whereas brain neurons, except for a very small number in the brainstem, lack CB 2 R expression (21).On the other hand, we recently reported that brain CB 2 Rs modulate cocaine self-administration and cocaine-induced increases in locomotion and extracellular dopamine (DA) in the nucleus accumbens in mice (22). This finding is supported by recent studies demonstrating that systemic administration of the CB 2 R agonist O-1966 inhibited cocaine-induced conditioned place preference in WT mice, but not in CB 2 −/− mice (23), and that increased CB 2 R expression in mouse brain attenuates cocaine self-administration and cocaine-enhanced locomotion (19). In addition, brain CB 2 Rs may be involved in several DA-related CNS disorders, such as Parkinson's disease (24), schizophrenia (25), anxiety (26), and depression (27). The cellular mechanisms underlying CB 2 R modulation of DA-related behav...

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“…RT-PCR-Total cellular RNA was isolated from HEK-293T, SH-SY5Y, SK-N-MC, or NG108-15 cells using the QuickPrep total RNA extraction kit (Amersham Biosciences) or from Macaca fascicularis spleen using TRIzol reagent (Invitrogen) as described previously (38). Total RNA (1 g) was reverse-transcribed by random priming using Moloney murine leukemia virus reverse transcriptase, RNase H minus, and point mutant, following the protocol of two-step RT-PCR provided by Promega (Madison, WI).…”

Section: Fusion Proteins and Expression Vectors-mentioning

confidence: 99%

“…We used this heteromer characteristic to further test for the expression of CB 1 -CB 2 receptor heteromers in rat brains. We selected globus pallidus slices for these experiments because it has been described that globus pallidus expresses a high amount of CB 2 receptor (38). The Akt/PKB and ERK1/2 phosphorylation was determined in slices as indicated under "Materials and Methods."…”

Section: Characterization Of Cb 1 -Cbmentioning

confidence: 99%

Cannabinoid Receptors CB1 and CB2 Form Functional Heteromers in Brain

Callén

Moreno

Barroso‐Chinea

et al. 2012

Journal of Biological Chemistry

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207

141

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Background: Although CB 1 , the most abundant neuronal receptors, and CB 2 receptors are co-expressed in neurons, the CB 1 -CB 2 relationship is unknown. Results: CB 1 and CB 2 receptors form heteromers in neuronal cells and in the brain. Conclusion: Activation of either receptor leads to negative modulation of the partner receptor via heteromers. Significance: These heteromers may explain previous conflicting results and serve as therapeutic targets.

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Expression of the mRNA coding the cannabinoid receptor 2 in the pallidal complex of Macaca fascicularis

Cited by 127 publications

References 42 publications

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Cannabinoid CB ₂ receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice

Cannabinoid Receptors CB1 and CB2 Form Functional Heteromers in Brain

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Expression of the mRNA coding the cannabinoid receptor 2 in the pallidal complex of Macaca fascicularis

Cited by 127 publications

References 42 publications

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Cannabinoid CB 2 receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice

Cannabinoid Receptors CB1 and CB2 Form Functional Heteromers in Brain

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Cannabinoid CB ₂ receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice