New research out of the US, published online in the Proceedings of the National Academy of Sciences, suggests that changes to the brain’s circuitry brought on by stress may lead to cocaine-use relapse.

Changes to the circuitry are related to the regulation of serotonin—the neurotransmitter that regulates mood, appetite, sleep, muscle contraction, and some cognitive functions as memory and learning. Changes to serotonin levels in the studied mice, it is believe, causes low moods, thus triggering the drug-seeking behaviour.

Until recently, it was commonly believed that dopamine regulated drug seeking, by affecting the area of the brain where the motivation and reward seeking is controlled. It was believed that stress caused the prevention of dopamine in the brain, making the mice feel miserable. Resulting drug-seeking behaviours were thought to be an aversive response to the reduction in dopamine—an aversion to the negative feelings.

Scientists were quite surprised then to see adverse effects of stress converging on the region of the brain where serotonin-using nerves are located.

Dopamine-deficient bred mice, or mice with continuous ‘low moods’, continued to respond to stress-inducing scenarios with aversive behavior. When the scientists were able to deactivate the receptors in the serotonin-rich area of the brain, where there was much activity, they were able to effectively stop the aversive response and cocaine-seeking behaviors in the mice.

Researchers concluded that activation of receptors in the serotonin-rich area of the brain, either through pharmaceuticals or a stress-evoking trigger, may regulate the serotonin system. Furthermore, it may be possible to regulate drug-seeking behaviours through regulation of this system.

The findings, although very preliminary with a number of other factors still needing investigaton, the evidence is interesting for relapse prevention as manipulation of the brain’s serotonin levels could, theoretically, control the re-ignition of drug-seeking impulses.

By the same accord, earlier in October at Neuroscience 2009, the annual meeting of the Society for Neuroscience, findings on amino acid’s effect on cocaine addiction were presented. This study showed that the amino acid derivative NAC reverses changes to the brain’s circuitry made by cocaine addiction.

With advanced brain imaging, scientists can now map what occurs when the brain is exposed to drug-associated cues—or craving triggers. Cocaine, it was found, causes imbalances in the circuits regulating reward and cognitive control.

NAC, on the other hand, seemed to return normal function to the circuits of previously cocaine-addicted rats. Furthermore, after having received the amino acid, the rats did not return to their drug seeking behaviours, even while in the presence of drug cues.

Currently, a phase III clinical trial of NAC is underway. Findings could lead to an extremely useful biomedical treatment and relapse-prevention option.