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Title: Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption

Abstract

The anatomical proximity of the cannabinoid type 1 (CNR1/CB1R) and the dopamine D2 receptors (DRD2), their ability to form CB1R-DRD2 heteromers, their opposing roles in locomotion, and their involvement in ethanol's reinforcing and addictive properties prompted us to study the levels and distribution of CB1R after chronic ethanol intake, in the presence and absence of DRD2. We monitored the drinking patterns and locomotor activity of Drd2+/+ and Drd2-/- mice consuming either water or a 20% (v/v) ethanol solution (forced ethanol intake) for 6 months and used the selective CB1 receptor antagonist [{sup 3}H]SR141716A to quantify CB1R levels in different brain regions with in vitro receptor autoradiography. We found that the lack of DRD2 leads to a marked upregulation (approximately 2-fold increase) of CB1R in the cerebral cortex, the caudate-putamen, and the nucleus accumbens, which was reversed by chronic ethanol intake. The results suggest that DRD2-mediated dopaminergic neurotransmission and chronic ethanol intake exert an inhibitory effect on cannabinoid receptor expression in cortical and striatal regions implicated in the reinforcing and addictive properties of ethanol.

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
BROOKHAVEN NATIONAL LABORATORY (BNL)
Sponsoring Org.:
NATIONAL INSTITUTE ON ALCOHOL ABUSE & ALCOHOLISM
OSTI Identifier:
1014348
Report Number(s):
BNL-94761-2011-JA
Journal ID: ISSN 0145-6008; ACRSDM; YN0100000; TRN: US201111%%301
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Alcoholism: Clinical and Experimental Research; Journal Volume: 35; Journal Issue: 1
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AUTORADIOGRAPHY; BRAIN; CEREBRAL CORTEX; DISTRIBUTION; DOPAMINE; ETHANOL; IN VITRO; MICE; WATER; Cannabinoid; CB1; Dopamine; D2; Knockout; Ethanol; Autoradiography; PET

Citation Formats

Thanos, P.K., Wang, G., Thanos, P.K., Gopez, V., Delis, F., Michaelides, M., Grand, D.K., Wang, G.-J., Kunos, G., and Volkow, N.D. Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption. United States: N. p., 2011. Web. doi:10.1111/j.1530-0277.2010.01318.x.
Thanos, P.K., Wang, G., Thanos, P.K., Gopez, V., Delis, F., Michaelides, M., Grand, D.K., Wang, G.-J., Kunos, G., & Volkow, N.D. Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption. United States. doi:10.1111/j.1530-0277.2010.01318.x.
Thanos, P.K., Wang, G., Thanos, P.K., Gopez, V., Delis, F., Michaelides, M., Grand, D.K., Wang, G.-J., Kunos, G., and Volkow, N.D. Sat . "Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption". United States. doi:10.1111/j.1530-0277.2010.01318.x.
@article{osti_1014348,
title = {Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption},
author = {Thanos, P.K. and Wang, G. and Thanos, P.K. and Gopez, V. and Delis, F. and Michaelides, M. and Grand, D.K. and Wang, G.-J. and Kunos, G. and Volkow, N.D.},
abstractNote = {The anatomical proximity of the cannabinoid type 1 (CNR1/CB1R) and the dopamine D2 receptors (DRD2), their ability to form CB1R-DRD2 heteromers, their opposing roles in locomotion, and their involvement in ethanol's reinforcing and addictive properties prompted us to study the levels and distribution of CB1R after chronic ethanol intake, in the presence and absence of DRD2. We monitored the drinking patterns and locomotor activity of Drd2+/+ and Drd2-/- mice consuming either water or a 20% (v/v) ethanol solution (forced ethanol intake) for 6 months and used the selective CB1 receptor antagonist [{sup 3}H]SR141716A to quantify CB1R levels in different brain regions with in vitro receptor autoradiography. We found that the lack of DRD2 leads to a marked upregulation (approximately 2-fold increase) of CB1R in the cerebral cortex, the caudate-putamen, and the nucleus accumbens, which was reversed by chronic ethanol intake. The results suggest that DRD2-mediated dopaminergic neurotransmission and chronic ethanol intake exert an inhibitory effect on cannabinoid receptor expression in cortical and striatal regions implicated in the reinforcing and addictive properties of ethanol.},
doi = {10.1111/j.1530-0277.2010.01318.x},
journal = {Alcoholism: Clinical and Experimental Research},
number = 1,
volume = 35,
place = {United States},
year = {Sat Jan 01 00:00:00 EST 2011},
month = {Sat Jan 01 00:00:00 EST 2011}
}