drugs cause addiction by remodeling brain

Drugs may cause addiction by 'remodelling' brain by Marlowe Hood
Wed Apr 25, 2:16 PM ET



A heroin addict aching for a fix years after kicking the habit is not simply weak-willed but may be tormented by enduring changes in the brain caused by the drug itself, according a groundbreaking study released Wednesday.

In experiments carried out on rats, a team of American researchers at Brown University in Rhode Island showed that even a single dose of morphine physically altered the neural pathways that regulate the sensation of craving.

The change persisted long after the effects of the drug had worn off.

The study, published in the British journal Nature, adds weight to a new theory that sees addiction as a disease which "remodels" brain mechanisms related to learning and memory, the lead author, cellular physiologist Julie Kauer, said in an interview.

The findings also point the way to the tantalizing possibility of a pharmaceutical antidote to addiction, she added.

Kauer's experiments focused on the activity of synapses, the connective junction between brain cells.

So-called excitatory synapses increase the flow of chemicals -- such as dopamine, associated with a feeling of euphoria -- while inhibitory synapses impede such flows.

"You have to have both, because they create checks and balances on the system," she explained.

Previous studies have shown that excitatory synapses are strongly linked to building one's capacity for memory, and that -- just like muscles in the body -- they grow stronger over time with increased activity.

This is a virtuous circle when it comes to learning because the release of small amounts of dopamine creates the incentive to learn more. It also helps hone basic survival instincts.

But the same mechanism becomes a dangerous magnet for abuse when certain drugs such as heroin and cocaine provoke a similar response.

"If you have ever been really, really thirsty, that same craving may be the same thing that is going on in the brain of someone who is addicted to a drug," Kauer said.

In this context, she added, "addiction is a form of pathological learning" in which the brain has created a rewards system for something that is harmful to the body.

"I would not call it damage -- the circuit is working the way it should. But it has been remodelled in a maladaptive way," said Kauer.

The Nature study breaks new ground in two areas. It presents the strongest evidence to date that inhibitory synapses are also capable of "long-term potentiation", or LTP, the ability to strengthen and change over time.

And it showed that morphine, an opiate, continued to block LTP long after the drug was absent from the animal's system.

"The fact that they are long lasting could be one of the reasons that the craving for drugs is so hard to conquer, and suggests that addictive drugs are producing persistent physical changes," she said.

The study also points to the intriguing possibility of a pharmaceutical treatment to neutralize intense cravings, which could help those fighting addiction to resist the temptation of relapse.

It could likewise help prevent unwanted side effects of morphine in hospitals, where the opiate is frequently used as a painkiller.

The molecule disabled by the morphine is called guanylate cyclase. By pinpointing it, Kauer and her team identified a promising target for new drugs that could potentially prevent or treat addiction.

Such a treatment, however, might create other problems, she acknowledged. A remedy that removes a drug's addictive quality but not its capacity to provoke euphoria could add a temptation of another kind.