The Brain on Cocaine

There is a large array of studies focusing on how cocaine impacts the brain creating addiction. The main investigated mechanism has been the effect of cocaine on dopamine (the feel good or reward hormone) and dopamine transporters, proteins that reabsorb this neurotransmitter once it has sent its signal. Cocaine is known to inactivate dopamine transporters, so that the dopamine keeps hanging around, creating a sensation of excitement.

But a new research made at the U.S. Department of Energy's Brookhaven National Laboratory and published in the journal "Synapse" shows that cocaine's effects appear beyond the dopamine system in mice devoid of the gene encoding 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 lead researcher Panayotis Thanos, a neuroscientist at Brookhaven.

Positron emission tomography (PET) scanning assessed brain metabolism in dopamine-transporter-deficient mice (DAT knockouts) and in mice with normal dopamine transporter gene. The mice received a radioactive type of glucose (the fuel used by brain) with the food and PET scanners localized glucose amounts in different brain areas.

Brain scans were made on mice before and after cocaine administration, and also on mice receiving a saline solution instead of the drug. Normally, DAT mice had an increased metabolism in the thalamus and cerebellum compared to normal mice, connected to chronically increased amounts of dopamine. Those scans pointed that dopamine levels could be important in controlling glucose levels in those brain parts, crucial in processing sensory information, learning, and motor function.

"Interestingly, DAT knockout mice have been suggested as an animal model for attention-deficit hyperactivity disorder (ADHD). Elevated metabolism due to persistent elevated dopamine levels may be a factor contributing to the symptoms of ADHD," said Thanos.

Cocaine administration plummeted brain metabolism in both groups of mice, but much more in normal mice than in DAT knockouts. The decreased metabolism could be somehow connected with the cocaine-caused impairing of dopamine transporters, but a decrease in metabolism in the thalamus also took place in the DAT knockout mice.

This could be due to the impact of cocaine on other neurotransmitter systems, like norepinepherine or serotonin. Cocaine appeared to impact mainly the regional brain activity, whose main controller is dopamine, and to a secondary degree, norepinephrine or serotonin.