Cocaine's effects on brain metabolism may boost abuse

Washington, Feb 19 : A new study in mice conducted at the U.S. Department of Energy's Brookhaven National Laboratory has found that cocaine's effect is not just limited to the dopamine system, the brain's 'reward' chemical, it also has a significant effect on brain metabolism that might contribute to abuse.

Previous studies on cocaine addiction and efforts to block its addictiveness have focused on dopamine transporters, proteins that reabsorb the brain's 'reward' chemical once its signal is sent.

Since the drug blocks dopamine transporters from doing their recycling job, it leaves the feel-good chemical around to keep sending the pleasure signal.

Now, the new study has found that cocaine's effects go beyond the dopamine system.

In the study, cocaine had significant effects on brain metabolism, even in mice that lack the gene for dopamine transporters.

"In dopamine-transporter-deficient mice, these effects on metabolism are clearly independent of cocaine's effects on dopamine. These metabolic factors may be a strong regulator of cocaine use and abuse, and may also suggest new avenues for addiction treatments," said Brookhaven neuroscientist Panayotis (Peter) Thanos, who led the research.

To measure brain metabolism in dopamine-transporter deficient mice (known as DAT knockouts) and in littermates that had normal dopamine transporter levels, the researchers used positron emission tomography (PET scanning).

They tested the mice before and after cocaine administration, and compared the results to mice treated with saline instead of the drug.

Prior to any treatment, mice lacking dopamine transporters had significantly higher metabolism in the thalamus and cerebellum compared to normal mice.

After the researchers administered cocaine, whole brain metabolism decreased in both groups of mice, but more significantly in normal mice than in DAT knockouts.

The researchers were able to find this reduction in metabolism in a wide range of brain regions in the normal mice, suggesting that these decreases in metabolism are somehow linked to the blockade of dopamine transporters by cocaine.

They also found a reduction in metabolism in the thalamus region in the DAT knockout mice.

This effect might likely be due to the effect of cocaine on other neurotransmitter systems, for example, norepinepherine or serotonin.

In short, cocaine exposure has an effect on regional brain activity, which is mostly driven by dopamine action and to a secondary degree norepinephrine or serotonin.

The study will appear in the May 2008 issue of the journal Synapse.

ANI