Neuronal localization of cannabinoid receptors in the basal ganglia of the rat

Herkenham, Miles; Lynn, Allison B.; Costa, Brian R. de; Richfield, Eric K.

doi:10.1016/0006-8993(91)90970-7

Cited by 492 publications

(309 citation statements)

References 29 publications

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“…The labeling profile of the two antibodies was very similar, tagging primarily the neuropil and avoiding the neuronal cell bodies. Similar results were obtained using coronal sections of rat brain (results not shown), which agrees with previous reports (Herkenham et al, 1991;Hettinger et al, 2001). No immunostaining was found in samples from genetically modified CB 1 or A 2A knockout mice ( Figure 1c and d), which demonstrates the specificity of the primary antibodies.…”

Section: Competition Binding Assayssupporting

confidence: 92%

“…One of the most salient effects of CB 1 receptor activation is motor depression, which is related to the significant modulatory role played by endocannabinoids in the basal ganglia (Gough and Olley, 1978;Ledent et al, 1999;Sanudo-Pena et al, 1999;van der Stelt and Di Marzo, 2003). CB 1 receptors are abundantly expressed in different structures of the basal ganglia, including the striatum (Herkenham et al, 1991). In the striatum, CB 1 receptors are localized in both types of GABAergic efferent neurons, enkephalinergic and dynorphinergic (Hohmann and Herkenham, 2000;Fusco et al, 2004), which constitute more than 90% of the striatal neuronal population (Gerfen, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Striatal Adenosine A2A and Cannabinoid CB1 Receptors Form Functional Heteromeric Complexes that Mediate the Motor Effects of Cannabinoids

Carriba

Ortiz

Patkar

et al. 2007

Neuropsychopharmacol

222

219

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The mechanism of action responsible for the motor depressant effects of cannabinoids, which operate through centrally expressed cannabinoid CB 1 receptors, is still a matter of debate. In the present study, we report that CB 1 and adenosine A 2A receptors form heteromeric complexes in co-transfected HEK-293T cells and rat striatum, where they colocalize in fibrilar structures. In a human neuroblastoma cell line, CB 1 receptor signaling was found to be completely dependent on A 2A receptor activation. Accordingly, blockade of A 2A receptors counteracted the motor depressant effects produced by the intrastriatal administration of a cannabinoid CB 1 receptor agonist. These biochemical and behavioral findings demonstrate that the profound motor effects of cannabinoids depend on physical and functional interactions between striatal A 2A and CB 1 receptors.

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Section: Competition Binding Assayssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Striatal Adenosine A2A and Cannabinoid CB1 Receptors Form Functional Heteromeric Complexes that Mediate the Motor Effects of Cannabinoids

Carriba

Ortiz

Patkar

et al. 2007

Neuropsychopharmacol

222

219

View full text Add to dashboard Cite

show abstract

“…In human clinical applications, cannabinoid agonist drugs stimulate appetite in hypophagic patients, and conversely, cannabinoid antagonist drugs are currently of interest for potential therapeutic roles to suppress consumption as dieting aids and addiction treatments (Di Marzo and Petrocellis, 2006). Cannabinoid receptors (CB1 and/or CB2) are present throughout the limbic forebrain, including the striatum and nucleus accumbens (Herkenham et al, 1991;Moldrich and Wenger, 2000;Fusco et al, 2004;Gong et al, 2006). Many functional effects of endocannabinoids in brain are thought to occur via CB1 receptors (Piomelli, 2003).…”

Section: Introductionmentioning

confidence: 99%

Endocannabinoid Hedonic Hotspot for Sensory Pleasure: Anandamide in Nucleus Accumbens Shell Enhances ‘Liking’ of a Sweet Reward

Mahler

Smith

Berridge

2007

Neuropsychopharmacol

306

259

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Cannabinoid drugs such as D 9 -THC are euphoric and rewarding, and also stimulate food intake in humans and animals. Little is known about how naturally occurring endogenous brain cannabinoids mediate pleasure from food or other natural sensory rewards. The taste reactivity paradigm measures effects of brain manipulations on affective orofacial reactions to intraorally administered pleasant and unpleasant tastes. Here we tested if anandamide microinjection into medial nucleus accumbens shell enhances these affective reactions to sweet and bitter tastes in rats. Anandamide doubled the number of positive 'liking' reactions elicited by intraoral sucrose, without altering negative 'disliking' reactions to bitter quinine. Anandamide microinjections produced Fos plumes of approximately 0.02-1 mm 3 volume. Plume-based maps, integrated with behavioral data, identified the medial shell of accumbens as the anatomical hotspot responsible for hedonic amplification. Anandamide produced especially intense hedonic enhancement in a roughly 1.6 mm 3 'hedonic hotspot' in dorsal medial shell, where anandamide also stimulated eating behavior. These results demonstrate that endocannabinoid signals within medial accumbens shell specifically amplify the positive hedonic impact of a natural reward (though identification of the receptor specificity of this effect will require future studies). Identification of an endocannabinoid hotspot for sensory pleasure gives insight into brain mechanisms of natural reward, and may be relevant to understanding the neural effects of cannabinoid drugs of abuse and therapeutic agents.

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“…CB 1 receptors are densely expressed in the basal ganglia (Herkenham et al, 1990(Herkenham et al, , 1991Mailleux and Vanderhaeghen, 1992), where they regulate glutamatergic neurotransmission under both physiological and pathological conditions (see Romero et al, 2002, for review). The ability of CB 1 receptors to inhibit the synaptic release of glutamate in the striatum has been consistently reported (Gerdeman and Lovinger, 2001;Huang et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum

et al. 2006

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The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum AbstractThe ability of CB 1 receptors to regulate the release of glutamate in the striatum, together with the finding that, in experimental models of Huntington disease (HD), both endocannabinoid levels and CB 1 receptor densities are reduced, has prompted the investigation on the neuroprotective role of the cannabinoids in HD. Quinolinic acid (QA) is an excitotoxin that, when injected in the rat striatum reproduces many features of HD and that acts by stimulating glutamate outflow. The aim of the present study was to test the ability of the cannabinoid receptor agonist WIN 55,212-2 to prevent the effects induced by QA in the rat striatum. In microdialysis experiments, probe perfusion with WIN 55,212-2 significantly and dose-dependently prevented the increase in extracellular glutamate induced by QA. In electrophysiological recordings in corticostriatal slices, the application of WIN 55,212-2 prevented QA-induced reduction of the field potential amplitude. Both effects of WIN 55,212-2 were prevented by the CB 1 receptor antagonist AM 251. In in vivo experiments, intrastriatal WIN 55,212-2 significantly attenuated the striatal damage induced by QA, although no significant effects were observed on a behavioural ground.These data demonstrate that the stimulation of CB 1 receptors might lead to neuroprotective effects against excitotoxic striatal toxicity.

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Neuronal localization of cannabinoid receptors in the basal ganglia of the rat

Cited by 492 publications

References 29 publications

Striatal Adenosine A2A and Cannabinoid CB1 Receptors Form Functional Heteromeric Complexes that Mediate the Motor Effects of Cannabinoids

Striatal Adenosine A2A and Cannabinoid CB1 Receptors Form Functional Heteromeric Complexes that Mediate the Motor Effects of Cannabinoids

Endocannabinoid Hedonic Hotspot for Sensory Pleasure: Anandamide in Nucleus Accumbens Shell Enhances ‘Liking’ of a Sweet Reward

The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum

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