Localization of cannabinoid CB1 receptor mRNA in neuronal subpopulations of rat striatum: A double‐label in situ hybridization study

By A. Hohmann, M. Herkenham. 2000

196 citations recorded by the source corpus.

Double‐label in situ hybridization was used to identify the phenotypes of striatal neurons that express mRNA for cannabinoid CB1 receptors. Simultaneous detection of multiple mRNAs was performed by combining a 35S‐labeled ribonucleotide probe for CB1 mRNA with digoxigenin‐labeled riboprobes for striatal projection neurons (preprotachykinin A, prodynorphin, and preproenkephalin mRNAs) and interneurons (vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT), somatostatin, and glutamic acid decarboxylase (Mr 67,000; GAD67) mRNAs). To ascertain whether CB1 mRNA was a marker for striatal efferents, digoxigenin‐labeled probes for mRNA markers of both striatonigral (prodynorphin or preprotachykinin A mRNAs), and striatopallidal (proenkephalin mRNAs) projection neurons were combined with the 35S‐labeled probe for CB1. A mediolateral gradient in CB1 mRNA expression was observed at rostral and mid‐striatal levels; in the same coronal sections the number of silver grains per cell ranged from below the threshold of detectability at the medial and ventral poles to saturation at the dorsolateral boundary bordered by the corpus callosum. At the caudal level examined, CB1 mRNA was denser in the ventral sector relative to the dorsal sector. Virtually all neurons expressing mRNA markers for striatal projection neurons colocalized CB1 mRNA. Combining a 35S‐labeled riboprobe for CB1 with digoxigenin‐labeled riboprobes for both preproenkephalin and prodynorphin confirmed localization of CB1 mRNA to striatonigral and striatopallidal neurons expressing prodynorphin and preproenkephalin mRNAs, respectively. However, CB1 mRNA‐positive cells that failed to coexpress the other markers were also apparent. CB1 mRNA was localized to putative GABAergic interneurons that express high levels of GAD67 mRNA. These interneurons enable functional interactions between the direct and indirect striatal output pathways. By contrast, aspiny interneurons that express preprosomatostatin mRNA and cholinergic interneurons that coexpress ChAT and VAChT mRNAs were CB1 mRNA‐negative. The present data provide direct evidence that cannabinoid receptors are synthesized in striatonigral neurons that contain dynorphin and substance P and striatopallidal neurons that contain enkephalin. By contrast, local circuit neurons in striatum that contain somatostatin or acetylcholine do not synthesize cannabinoid receptors. Synapse 37:71–80, 2000. Published 2000 Wiley‐Liss, Inc.

Subfields: Cellular and Molecular Neuroscience, Pharmacology

View Paper: https://www.semanticscholar.org/paper/5c3299f70c5ff7deff6633b8877e615830659abf

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In Cellular and Molecular Neuroscience

1. John Polich
2. P. Pacher
3. S. Batkai
4. George Kunos
5. K. Mackie
6. Daniele Piomelli

In Pharmacology

1. P. Pacher
2. S. Batkai
3. George Kunos
4. K. Mackie
5. Daniele Piomelli
6. V. Di Marzo

Citations in the corpus

• Cannabinoid receptors and their ligands. (2002, unknown): “The presence of CB1 receptors on the terminals of striatal projection neurons is supported by results from in situ hybridization experiments in which CB1 mRNA was used as a marker.(16,114) Finally, in myenteric neurons of porcine and guinea-pig small intestine, CB1 immunostaining has been shown to b”
• The molecular logic of endocannabinoid signalling (2003, background): “, local-circuit GABA interneurons ('fast-spiking' interneurons that do not express CCK-8”
• The Endocannabinoid System as an Emerging Target of Pharmacotherapy (2006, background): “…are highly expressed in the basal ganglia, especially in the substantia nigra and in the cerebellum (Herkenham et al., 1990, 1991a,b; Mailleux and Vanderhaeghen, 1992; Tsou et al., 1998; Hohmann and Herkenham, 2000; Moldrich and Wenger, 2000; Howlett et al., 2002), areas involved in motor control.”
• Neuropsychology and neuropharmacology of P3a and P3b. (2006, background): “In the striatum, GABAergic interneurons expressing CB1 receptors play an important role regulating striatal output pathways (Hohmann and Herkenham, 2000).”
• Distribution of cannabinoid receptors in the central and peripheral nervous system. (2005, background): “CB1 receptors are present on both the striatonigral (prodynorphin or preprotachykinin A positive) and striatopallidal (proenkephalin positive) projection pathways (Hohmann and Herkenham 2000).”