11 March 2008

Brain wired for addiction?

Do the brain changes noted in drug addicts help cause their addiction, or are they the result of drug abuse?

Do the brain changes noted in drug addicts help cause their addiction, or are they the result of drug abuse?

A new study might solve that chicken-and-egg puzzle, pointing to new ways of preventing and treating addiction, researchers say.

The rat study suggests that "some individuals may be predisposed to the effects of cocaine on the brain", making them more likely to try the drug and become addicts, said lead researcher Dr Jeffrey Dalley, of Cambridge University's Behavioural and Clinical Neuroscience Institute in the United Kingdom.

Dopamine receptors implicated
Specifically, rats that went on to compulsively self-administer cocaine intravenously were more likely to have fewer brain cell surface receptors for the neurotransmitter dopamine in an area of the brain called the nucleus accumbens, compared to rodents that were less prone to addiction.

"The study is the first to conclusively demonstrate that changes in dopamine receptors in the nucleus accumbens pre-date cocaine use," Dalley said. That means that these brain changes are not caused by cocaine exposure but may encourage use of the drug.

The findings are published in the March 2 issue of Science.

A chicken-and-egg problem
Understanding the neurological changes that help trigger and sustain addiction is key to developing effective prevention and treatment. Numerous studies have noted a myriad differences in the brains of drug addicts versus healthy individuals, but "it's been basically impossible to know which ones were there before they started to take the drug and which were a consequence of the exposure to the drug," said Dr Nora Volkow, director of the US National Institute on Drug Abuse.

One brain change noted in many addicts - a paucity of dopamine receptors on cells in the nucleus accumbens - has been especially intriguing.

"The nucleus accumbens forms part of the basal ganglia, a series of interconnected brain structures involved in movement and motivated behaviour," Dalley explained. "The nucleus accumbens is considered by many to be the interface of motivation and behaviour. It has been extensively implicated in drug reward/addiction."

How the study was conducted
The Cambridge study focused on the brains of rats. Using high-tech PET brain scanning technology, they tracked dopamine activity in the nucleus accumbens of each rodent before the animals were exposed to a supply of cocaine.

The rats were then allowed to obtain cocaine intravenously. The researchers compared what they had seen in the PET scans to the rats' individual behaviours and propensity to cocaine abuse.

Dalley's team first noticed that rats with a trait they called "impulsivity" - a relative inability to resist new stimuli - were much more likely to compulsively self-administer cocaine compared to less-impulsive rats. These highly impulsive rats also had lower levels of D2 dopamine receptors on the cells of the nucleus accumbens - even before their first exposure to cocaine.

"Cocaine itself can reduce levels of this receptor," Dalley noted, but the rat experiment shows that addictive brains have low levels of D2 to begin with - effectively setting them up for drug abuse.

Human brains more complicated
"Human brains are obviously more complex than a rat brain, but there are many similarities in the ways in which rodent and human brains are organised," Dalley said, so it's not far-fetched to extrapolate these findings to people.

Volkow said the results are not surprising, since scientists have long known that low levels of dopamine receptors in the nucleus accumbens are linked to addiction and not just for cocaine. "In animal models, when you bring down the dopamine D2 receptors, those animals then have a vulnerability for taking a wide variety of drugs," she said.

But the finding that this D2 deficit appears before drug exposure could shed light on what causes addiction and point to new and better ways to fight it.

Impulsivity is the key
According to Dalley, people's tendency toward impulsivity appears to originate in the nucleus accumbens. So, when treating addiction, "it may be better to [first] treat impulsivity, which appears to lie at the heart of compulsive drug disorders". In fact, any increase in impulsivity may "be a trigger for relapse", according to Dalley. He said his team is already testing that theory.

Dr James Garbutt, a professor of psychiatry at the University of North Carolina, Chapel Hill, agreed that impulsivity is one key factor driving drug abuse. "We know that in humans, impulsive, disinhibited traits in young adolescence are also predictive of the likelihood of getting in trouble with drugs and alcohol," he said.

But Volkow believes addiction treatment will always be more complicated than just curbing risk-taking behaviours. "It's not just about impulsivity, there are multiple systems [involved]," she said. "In terms of therapy, we've come to realise that you need a multi-pronged approach. There's not going to be one single intervention that's going to be a miracle cure."

Only a predisposition
The UK findings certainly don't mean that low D2 levels "doom" specific people to substance abuse, Dalley added.

"We are talking about predisposition, a hidden vulnerability," he said. "There are many complex reasons why people engage in drug-taking behaviour. Low D2 receptors appears to be one trait marker that may or may not tip individuals into the downward spiral of drug addiction."

The study may even have implications for research into the prevention and treatment of attention-deficit hyperactivity disorder (ADHD). That's because impulsivity, and the activity of the nucleus accumbens, also figure highly in that condition, Dalley said.

"It therefore potentially offers a new model to investigate novel therapeutic strategies" for ADHD, Dalley said. – (HealthDayNews)

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