How cocaine takes the brakes off the brain

Cocaine messes around with the brain. That scientific no-brainer has been getting more focused over the years, as neuroscientists identify key circuitry that can be reshaped by addiction.

But an addiction researcher in Switzerland believes his colleagues may have been a bit too focused on the accelerator instead of the brakes – stimulation rather than disinhibition.

Cocaine interferes with a natural inhibitor holding a reward neurotransmitter in balance, and without that brake, an unrestrained flow of dopamine sets off circuitry changes that have been tied to addictive behavior, according to a study published online Thursday in the journal Science.

Dr. Christian Luscher, a neuroscientist at the University of Geneva, injected mice with cocaine and examined two brain areas: the nucleus accumbens, which is associated with reward, pleasure and reinforcement learning, and the ventral tegmental area, which is crucial to motivation and cognition. Both have been implicated in addiction, and much research has focused on how the nucleus accumbens excites neurons in the tegmental area that produce dopamine, a neurostransmitter.

But Luscher found that the accumbens predominantly targets neurons that produce another neurotransmitter, called GABA, which normally inhibits dopamine release.

“Because you inhibit an inhibitory neuron, what you end up with is that the dopamine neurons of the ventral tegmental area are more active,” Luscher said. “Under normal conditions, the dopamine neurons of the ventral tegmental area are under a constant inhibition, a brake, by these GABA neurons … and those are the targets of the neurons from the accumbens.”

Luscher said the mice data suggest this loss of a braking system is a cause of addictive behavior. He is pursuing the theory using deep brain stimulation in mice, a method he believes could easily be used therapeutically on humans.

“Why wouldn’t it be possible to use deep brain stimulation, an FDA-approved therapy for Parkinson’s, also for addiction?” Luscher said.

Luscher’s current research and the future stimulation studies rely on optogenetics, a technique developed at Stanford University that uses fiber-optics to stimulate activity on the cellular level.