Cannabinoid receptor localization in brain.
M Herkenham, A B Lynn, M D Little, M R Johnson, L S Melvin, B R De Costa, K C Rice
Proceedings of the National Academy of Sciences March 1990 DOI: 10.1073/pnas.87.5.1932 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Population | Brain sections from several mammalian species, including human |
| Interventions | [3H]CP 55 940 |
| Key points | The authors report that [3H]CP 55,940 labels a specific cannabinoid receptor whose binding affinities for natural and synthetic cannabinoids correlate with their potencies in biological assays, suggesting this receptor mediates cannabinoid effects including human subjective experience. Autoradiography shows a conserved brain distribution, densest in the substantia nigra pars reticulata and globus pallidus and in the hippocampus and cerebellum, with sparse lower brainstem binding that may explain the non-lethality of high delta 9-tetrahydrocannabinol doses. |
Abstract
[3H]CP 55,940, a radiolabeled synthetic cannabinoid, which is 10-100 times more potent in vivo than delta 9-tetrahydrocannabinol, was used to characterize and localize a specific cannabinoid receptor in brain sections. The potencies of a series of natural and synthetic cannabinoids as competitors of [3H]CP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in our in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience. Autoradiography of cannabinoid receptors in brain sections from several mammalian species, including human, reveals a unique and conserved distribution; binding is most dense in outflow nuclei of the basal ganglia--the substantia nigra pars reticulata and globus pallidus--and in the hippocampus and cerebellum. Generally high densities in forebrain and cerebellum implicate roles for cannabinoids in cognition and movement. Sparse densities in lower brainstem areas controlling cardiovascular and respiratory functions may explain why high doses of delta 9-tetrahydrocannabinol are not lethal.
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