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Role of endocannabinoids and cannabinoid CB1 receptors in alcohol-related behaviors.
Ann N Y Acad Sci. 2004 Oct; 1025:515-27.AN

Abstract

This review presents the remarkable research during the past several years indicating that some of the pharmacological and behavioral effects of alcohol, including alcohol drinking and alcohol-preferring behavior, are mediated through one of the most abundant neurochemical systems in the central nervous system, the endocannabinoid signaling system. The advances, with the discovery of specific receptors and the existence of naturally occurring cannabis-like substances in the mammalian system and brain, have helped in understanding the neurobiological basis for drugs of abuse, including alcoholism. The cDNA and genomic sequences encoding G-protein-coupled cannabinoid receptors (CB1 and CB2) from several species have now been cloned. This has facilitated discoveries of endogenous ligands (endocannabinoids). To date, two fatty acid derivatives characterized to be arachidonylethanolamide and 2-arachidonylglycerol have been isolated from both nervous and peripheral tissues. Both these compounds have been shown to mimic the pharmacological and behavioral effects of Delta9-tetrahydrocannabinol, the psychoactive component of marijuana. The involvement of the endocannabinoid signaling system in tolerance development to drugs of abuse, including alcohol, were unknown until recently. Studies from our laboratory demonstrated for the first time the downregulation of CB1 receptor function and its signal transduction by chronic alcohol. The observed downregulation of CB1 receptor binding and its signal transduction results from the persistent stimulation of receptors by the endogenous CB1 receptor agonists arachidonylethanolamide and 2-arachidonylglycerol, the synthesis of which is increased by chronic alcohol treatment. The deletion of CB1 receptor has recently been shown to block voluntary alcohol intake in mice, which is consistent with our previous findings where the DBA/2 mice known to avoid alcohol intake had significantly reduced brain CB1 receptor function. These findings suggest a role for the CB1 receptor gene in excessive alcohol drinking behavior and development of alcoholism. Ongoing investigations may lead to the development of potential therapeutic agents to modulate the endocannabinoid signaling system, which will be helpful for the treatment of alcoholism.

Authors+Show Affiliations

New York State Psychiatric Institute, New York 10032, USA. hungund@nki.rfmh.orgNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

15542757

Citation

Hungund, Basalingappa L., and Balapal S. Basavarajappa. "Role of Endocannabinoids and Cannabinoid CB1 Receptors in Alcohol-related Behaviors." Annals of the New York Academy of Sciences, vol. 1025, 2004, pp. 515-27.
Hungund BL, Basavarajappa BS. Role of endocannabinoids and cannabinoid CB1 receptors in alcohol-related behaviors. Ann N Y Acad Sci. 2004;1025:515-27.
Hungund, B. L., & Basavarajappa, B. S. (2004). Role of endocannabinoids and cannabinoid CB1 receptors in alcohol-related behaviors. Annals of the New York Academy of Sciences, 1025, 515-27.
Hungund BL, Basavarajappa BS. Role of Endocannabinoids and Cannabinoid CB1 Receptors in Alcohol-related Behaviors. Ann N Y Acad Sci. 2004;1025:515-27. PubMed PMID: 15542757.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of endocannabinoids and cannabinoid CB1 receptors in alcohol-related behaviors. AU - Hungund,Basalingappa L, AU - Basavarajappa,Balapal S, PY - 2004/11/16/pubmed PY - 2005/2/19/medline PY - 2004/11/16/entrez SP - 515 EP - 27 JF - Annals of the New York Academy of Sciences JO - Ann N Y Acad Sci VL - 1025 N2 - This review presents the remarkable research during the past several years indicating that some of the pharmacological and behavioral effects of alcohol, including alcohol drinking and alcohol-preferring behavior, are mediated through one of the most abundant neurochemical systems in the central nervous system, the endocannabinoid signaling system. The advances, with the discovery of specific receptors and the existence of naturally occurring cannabis-like substances in the mammalian system and brain, have helped in understanding the neurobiological basis for drugs of abuse, including alcoholism. The cDNA and genomic sequences encoding G-protein-coupled cannabinoid receptors (CB1 and CB2) from several species have now been cloned. This has facilitated discoveries of endogenous ligands (endocannabinoids). To date, two fatty acid derivatives characterized to be arachidonylethanolamide and 2-arachidonylglycerol have been isolated from both nervous and peripheral tissues. Both these compounds have been shown to mimic the pharmacological and behavioral effects of Delta9-tetrahydrocannabinol, the psychoactive component of marijuana. The involvement of the endocannabinoid signaling system in tolerance development to drugs of abuse, including alcohol, were unknown until recently. Studies from our laboratory demonstrated for the first time the downregulation of CB1 receptor function and its signal transduction by chronic alcohol. The observed downregulation of CB1 receptor binding and its signal transduction results from the persistent stimulation of receptors by the endogenous CB1 receptor agonists arachidonylethanolamide and 2-arachidonylglycerol, the synthesis of which is increased by chronic alcohol treatment. The deletion of CB1 receptor has recently been shown to block voluntary alcohol intake in mice, which is consistent with our previous findings where the DBA/2 mice known to avoid alcohol intake had significantly reduced brain CB1 receptor function. These findings suggest a role for the CB1 receptor gene in excessive alcohol drinking behavior and development of alcoholism. Ongoing investigations may lead to the development of potential therapeutic agents to modulate the endocannabinoid signaling system, which will be helpful for the treatment of alcoholism. SN - 0077-8923 UR - https://www.unboundmedicine.com/medline/citation/15542757/Role_of_endocannabinoids_and_cannabinoid_CB1_receptors_in_alcohol_related_behaviors_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0077-8923&date=2004&volume=1025&spage=515 DB - PRIME DP - Unbound Medicine ER -