| Cannabinoids excite circadian clock neurons. | |
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MedLine Citation:
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PMID: 20668190 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cannabinoids, the primary active agent in drugs of abuse such as marijuana and hashish, tend to generate a distorted sense of time. Here we study the effect of cannabinoids on the brain's circadian clock, the suprachiasmatic nucleus (SCN), using patch clamp and cell-attached electrophysiological recordings, RT-PCR, immunocytochemistry, and behavioral analysis. The SCN showed strong expression of the cannabinoid receptor CB1R, as detected with RT-PCR. SCN neurons, including those using GABA as a transmitter, and axons within the SCN, expressed CB1R immunoreactivity. Behaviorally, cannabinoids did not alter the endogenous free-running circadian rhythm in the mouse brain, but did attenuate the ability of the circadian clock to entrain to light zeitgebers. In the absence of light, infusion of the CB1R antagonist AM251 caused a modest phase shift, suggesting endocannabinoid modulation of clock timing. Interestingly, cannabinoids had no effect on glutamate release from the retinohypothalamic projection, suggesting a direct action of cannabinoids on the retinohypothalamic tract was unlikely to explain the inhibition of the phase shift. Within the SCN, cannabinoids were excitatory by a mechanism based on presynaptic CB1R attenuation of axonal GABA release. These data raise the possibility that the time dissociation described by cannabinoid users may result in part from altered circadian clock function and/or entrainment to environmental time cues. |
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Authors:
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Claudio Acuna-Goycolea; Karl Obrietan; Anthony N van den Pol |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 30 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-29 Completed Date: 2010-08-20 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 10061-6 Citation Subset: IM |
Affiliation:
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Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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6-Cyano-7-nitroquinoxaline-2,3-dione
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pharmacology Action Potentials / drug effects, physiology Adaptation, Ocular / drug effects, physiology Analgesics / pharmacology Analysis of Variance Animals Animals, Newborn Behavior, Animal / drug effects, physiology Benzoxazines / pharmacology Biophysics / methods Cannabinoids / genetics, metabolism* Circadian Rhythm / drug effects, physiology* Electric Stimulation / methods Excitatory Amino Acid Antagonists / pharmacology Excitatory Postsynaptic Potentials / drug effects Gene Expression Regulation / drug effects, physiology Glutamate Decarboxylase / metabolism Green Fluorescent Proteins / genetics Male Mice Mice, Transgenic Morpholines / pharmacology Motor Activity / drug effects, physiology Naphthalenes / pharmacology Neurons / drug effects, physiology* Patch-Clamp Techniques / methods Piperidines / pharmacology Pyrazoles / pharmacology Receptor, Cannabinoid, CB1 / genetics, metabolism Suprachiasmatic Nucleus / cytology* Tetrodotoxin Valine / analogs & derivatives, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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MH62335/MH/NIMH NIH HHS; NS 067409/NS/NINDS NIH HHS; NS34887/NS/NINDS NIH HHS; NS48476/NS/NINDS NIH HHS; R01 DK084052-01A1/DK/NIDDK NIH HHS; R01 NS034887-13/NS/NINDS NIH HHS; R01 NS041454-09/NS/NINDS NIH HHS; R01 NS048476-07/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/AM 251; 0/Analgesics; 0/Benzoxazines; 0/Cannabinoids; 0/Excitatory Amino Acid Antagonists; 0/Morpholines; 0/Naphthalenes; 0/Piperidines; 0/Pyrazoles; 0/Receptor, Cannabinoid, CB1; 115066-14-3/6-Cyano-7-nitroquinoxaline-2,3-dione; 134959-51-6/Win 55212-2; 147336-22-9/Green Fluorescent Proteins; 4368-28-9/Tetrodotoxin; 7004-03-7/Valine; 76326-31-3/2-amino-5-phosphopentanoic acid; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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