Methamphetamine addiction appears to be hard to kick mainly because there are some irreversible changes in the dopamine-releasing machinery in the brain, a new mice study has indicated.
Dopamine is one of the brain's major neurotransmitters.
The research team, led by Nigel Bamford, of the University of Washington, Seattle, treated mice with methamphetamine and examined how prolonged exposure to the drug affected dopamine levels.
The researchers focused on the dopamine machinery in the brain's corticostriatal region, which is believed to have the "habit" circuitry that plays a major role in the compulsive drug seeking seen in people addicted to methamphetamine and amphetamine.
The results showed that extended exposure to methamphetamine caused a depression of the synaptic dopamine machinery in the corticostriatal region that lasted for months after the mice were no longer given the drug.
However, a dose of methamphetamine reversed the depressive effects on the synaptic dopamine machinery, they discovered.
The researchers also found that the drug produced its long-term effect by altering specific types of receptors for dopamine and another neurotransmitter called acetylcholine.
The team concluded that the mechanism they identified "might provide a synaptic basis that underlies addiction and habit learning and their long-term maintenance."
Although other teams have revealed aspects of this puzzle previously, Bamford says this is the first time the pieces have been pulled together into a single study.
"It definitely does tie everything together," said Stephanie Borgland of the University of British Columbia in Vancouver, Canada.
Although methamphetamine seems to be particularly addictive, Bamford expects the same basic mechanism to apply to other addictive stimulants, including cocaine.
Bamford is now planning further studies of the interneurons.
"That's really where the [addiction] 'switch' is," he said.
The study is published in the April 10 issue of the journal Neuron.