Feature: The neuroscience of addiction

“I hadn’t had a smoke in nine months, and I was in the corner shop when a bloke in front of me bought a packet of cigarettes. I was surprised when someone else asked for a packet of Rothmans, and then I realised it was me.” – Smoker, 54.

It’s called “kicking the habit,” but every addict knows that after years or even decades of abstinence, casual exposure to some familiar cue associated with their former habit can kick them into a relapse.

Chronic addiction to legal or illicit drugs imposes huge costs on individuals, families and society, says Florey Neuroscience Institutes’ Professor Andrew Lawrence. New therapies to break the cycle and prevent former addicts relapsing into drug-taking could save governments billions of dollars in the costs of ill health, injury, lost productivity and criminal acts to fund illicit drug purchases.

According to Lawrence, susceptibility to relapse likely involves persistent changes in the brain’s neural circuitry. “From a human clinical perspective, the big problem with addiction of any form is that it’s a chronic disorder, characterised by persistent vulnerability to relapse,” he says.

“When I talk to lay audiences, the example I use is that everyone knows someone who has repeatedly tried to stop smoking, only to take it up again. That’s addiction in a nutshell. Addiction to nicotine is a chronic, relapsing brain disorder. The smoker knows they should give it up for their health, but part of their brain is telling them to carry on.

“We’re really interested in understanding the mechanisms behind drug-seeking. If we can understand those mechanisms, the neural pathways and chemicals mediating drug seeking, it could lead us to therapeutic targets that may be of greater value than those currently available.”

In their search for the molecular roots of addiction, the Florey team studied neurons that project from the prefrontal cortex, just behind the forehead, down into the striatum, in the inside of the forebrain. Within the striatum lies the nucleus accumbens, a cluster of neurons known to play a key role in reward, pleasure and addiction.

The neurons projecting from the prefrontal cortex employ the brain’s primary excitatory neurotransmitter glutamate. Where they terminate in the nucleus accumbens, the target neurons are studded with a type of glutamate receptor called mGlu5, also known as the metabotropic glutamate receptor 5.

“There is increasing evidence that this corticostriatal projection is a key part of the addictive system in laboratory animals, and some brain imaging studies in humans essentially concur with that conclusion,” says Lawrence.

Read part II of the neuroscience of addiction.

Read part III of the neuroscience of addiction.