Findings suggest that enzyme may be manipulated pharmacologically to control brain receptor
by Jessica Whiteside
Jan. 20, 2004 -- The discovery of a molecular "addiction switch" in the mammalian brain has the potential to control the addiction process in drug addicts, say U of T researchers.
A study published Jan. 18 in the online edition of Nature Neuroscience finds that a region of the brain called the VTA contains receptors that, when exposed to a certain enzyme, can control the switch from an addicted to non-addicted state and back again. This goes against previous ideas that viewed drug addiction as a permanent change in the brain, says lead author Steven Laviolette who conducted the research while a PhD student at U of T's Department of Anatomy and Cell Biology with senior author Professor Derek van der Kooy.
"Our findings suggest that instead of a permanent alteration in the brain, there's actually a switch that goes on between two separate systems (one that mediates the brain's response to drugs while not yet addicted and the other that mediates response once addicted)," says Laviolette. "They also suggest we may be able to manipulate that switch pharmacologically to take drug addicts back to a non-addicted state in a relatively short period of time so they do not crave the drug."
The switch is a brain receptor known as GABA-A; an enzyme - carbonic anhydrase - produced by the body controls how the receptor behaves. In studies with rats, the researchers were able to manipulate the enzyme with a drug to control whether it turned this switch on or off. Without such intervention, the brain can switch back to a non-addicted state following a period of withdrawal from drugs - a process often measured in weeks. By manipulating the enzyme pharmacologically, however, that return to a non-addicted state in rats has been reduced to a matter of hours, says Laviolette, now a post-doctoral fellow at the University of Pittsburgh.
"The same anatomical pathways that we're manipulating in rats also exist in humans so we hope that this will be applicable to human drug addiction as well," he says.
Collaborators on the study, funded by the Canadian Institutes of Health Research, included Roger Gallegos and Steven Henriksen of the Scripps Research Institute in California.