Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption
Article first published online: 19 OCT 2010
Copyright © 2010 by the Research Society on Alcoholism. No claim to original U.S. government works
Alcoholism: Clinical and Experimental Research
Volume 35, Issue 1, pages 19–27, January 2011
How to Cite
Thanos, P. K., Gopez, V., Delis, F., Michaelides, M., Grandy, D. K., Wang, G.-J., Kunos, G. and Volkow, N. D. (2011), Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption. Alcoholism: Clinical and Experimental Research, 35: 19–27. doi: 10.1111/j.1530-0277.2010.01318.x
- Issue published online: 17 DEC 2010
- Article first published online: 19 OCT 2010
- Received for publication November 25, 2009; accepted June 22, 2010.
Background: 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.
Methods: 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 [3H]SR141716A to quantify CB1R levels in different brain regions with in vitro receptor autoradiography.
Results: 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.
Conclusions: 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.