QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.085779v1 314/2/780    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hamelink, C. Articles by Eskay, R. L. Search for Related Content PubMed PubMed Citation Articles by Hamelink, C. Articles by Eskay, R. L.

NEUROPHARMACOLOGY

Comparison of Cannabidiol, Antioxidants, and Diuretics in Reversing Binge Ethanol-Induced Neurotoxicity

Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health (C.H., A.H., L.E.E.); Section of Neurochemistry and Neuroendocrinology, Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism (R.L.E.); and Radiology and Biology Branch, National Cancer Institute (D.A.W.), National Institutes of Health, Bethesda, Maryland

Binge alcohol consumption in the rat induces substantial neurodegeneration in the hippocampus and entorhinal cortex. Oxidative stress and cytotoxic edema have both been shown to be involved in such neurotoxicity, whereas N-methyl-D-aspartate (NMDA) receptor activity has been implicated in alcohol withdrawal and excitoxic injury. Because the nonpsychoactive cannabinoid cannabidiol (CBD) was previously shown in vitro to prevent glutamate toxicity through its ability to reduce oxidative stress, we evaluated CBD as a neuroprotectant in a rat binge ethanol model. When administered concurrently with binge ethanol exposure, CBD protected against hippocampal and entorhinal cortical neurodegeneration in a dose-dependent manner. Similarly, the common antioxidants butylated hydroxytoluene and -tocopherol also afforded significant protection. In contrast, the NMDA receptor antagonists dizocilpine (MK-801) and memantine did not prevent cell death. Of the diuretics tested, furosemide was protective, whereas the other two anion exchanger inhibitors, L-644,711 [(R)-(+)-(5,6-dichloro2,3,9,9a-tetrahydro 3-oxo-9a-propyl-1H-fluoren-7-yl)oxy acetic acid] and bumetanide, were ineffective. In vitro comparison of these diuretics indicated that furosemide is also a potent antioxidant, whereas the nonprotective diuretics are not. The lack of efficacy of L-644,711 and bumetanide suggests that the antioxidant rather than the diuretic properties of furosemide contribute most critically to its efficacy in reversing ethanol-induced neurotoxicity in vitro, in our model. This study provides the first demonstration of CBD as an in vivo neuroprotectant and shows the efficacy of lipophilic antioxidants in preventing binge ethanol-induced brain injury.

Address correspondence to: Dr. Robert Eskay, Bldg. 49, Room 5A-35, 9000 Rockville Pike, Bethesda, MD 20892. E-mail: bobsk{at}mail.nih.gov

This article has been cited by other articles:

				F. T. Crews and K. Nixon Mechanisms of Neurodegeneration and Regeneration in Alcoholism Alcohol Alcohol., March 1, 2009; 44(2): 115 - 127. [Abstract] [Full Text] [PDF]

				D. Ryan, A. J. Drysdale, C. Lafourcade, R. G. Pertwee, and B. Platt Cannabidiol Targets Mitochondria to Regulate Intracellular Ca2+ Levels J. Neurosci., February 18, 2009; 29(7): 2053 - 2063. [Abstract] [Full Text] [PDF]

				M. Rajesh, P. Mukhopadhyay, S. Batkai, G. Hasko, L. Liaudet, V. R. Drel, I. G. Obrosova, and P. Pacher Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H610 - H619. [Abstract] [Full Text] [PDF]

				E. Gouzoulis-Mayfrank and J. Daumann The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview J Psychopharmacol, March 1, 2006; 20(2): 188 - 193. [Abstract] [PDF]

				M. Y. Covarrubias, R. L. Khan, R. Vadigepalli, J. B. Hoek, and J. S. Schwaber Chronic alcohol exposure alters transcription broadly in a key integrative brain nucleus for homeostasis: the nucleus tractus solitarius Physiol Genomics, December 14, 2005; 24(1): 45 - 58. [Abstract] [Full Text] [PDF]