"Stopping alcohol abuse will never be as simple as turning on or off a 'switch,' but finding ways to modulate the brain's reward circuits could play a role in developing successful treatments," said Brookhaven's Panayotis (Peter) Thanos, lead author of both studies. The studies appear in the May 27, 2005, issue of Life Sciences and the June 2005 issue of Pharmacology Biochemistry and Behavior, both now available online.
In the first study, the scientists increased the number of dopamine "D2" receptors in strains of mice with genetically varying levels of D2 receptors. Earlier Brookhaven studies have shown that "up-regulating" D2 receptors by delivering the D2 gene directly to the brain's reward center decreased drinking behavior in rats trained (see: http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr090501.htm) or genetically predisposed (http://www.bnl.gov/bnlweb/pubaf/pr/PR_display.asp?prID=04-47) to drink large quantities of alcohol.
The Life Sciences study demonstrates this same "alcoholism-quenching" effect of D2 "gene therapy" in mice with normal to moderately low levels of D2s, supporting the idea that receptor up-regulation could play a role in the treatment of alcoholism.
Also in that study, however, so-called "knockout" mice, which initially had no D2s, drank more in response to D2 up-regulation. "This suggests that there may be a threshold level of D2 receptors needed for animals to respond to the reinforcing effects of alcohol," Thanos said.
Contact: Karen McNulty Walsh
DOE/Brookhaven National Laboratory