AMPHETAMINE and cocaine may limit the ability of brain cells to form new connections, even after people have stopped using the drug, a study on animals suggests. The finding could explain why some former drug users do badly at cognitive and behavioural tests.
When we experience something new, the neurons in the brain form new connections by growing longer and more branched extensions known as dendrites. It has been shown that amphetamines, cocaine and nicotine can cause neurons to grow in a similar way. So a team of researchers in Canada and the US wondered if taking drugs could interfere with the brain’s ability to respond to new experiences.
The researchers, based at the University of Lethbridge in Alberta and the University of Michigan in Ann Arbor, injected rats with a dose a day of either amphetamine or cocaine for 20 days, while a control group was injected only with saline. Then they put some of the rats in a rich, interesting environment – cages with toys, ramps and other rats – and left the others in isolated cages. After 14 weeks they examined cells from the neocortex and the nucleus accumbens, two portions of the brain that had been shown to respond to both experience and drugs.
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As they expected, rats from the control group showed more dendritic growth when placed in a rich environment than in plain cages. Those given amphetamine and raised in plain cages also showed dendritic growth. But rats raised in a rich environment after being given amphetamine did not show any more dendritic growth than those given the drug and raised in plain cages.
It may be that the rats’ neurons had reached their developmental limit. But rats given ever higher doses of amphetamine show ever more neuronal growth. More likely is that the amphetamine inhibited further development triggered by the rich environment.
When the team repeated the experiments with cocaine they found that 3 months after the last dose of cocaine, rats in both plain and rich cages showed no change in dendritic growth. Again, that suggests that the cocaine prevented the rats in the rich cages from forming more connections (Proceedings of the National Academy of Sciences, DOI: 10.1073 pnas.1834271100).
So why didn’t the cocaine cause any dendritic growth? Previous studies have shown growth after one month, so apparently by three months the cocaine-induced growth had reversed itself.
Bryan Kolb, one of the members of the team, says the next experiment will be to see if the drug-treated rats show any behavioural or cognitive changes. Studies on people who formerly used drugs suggests that the rats will show some cognitive impairment.
It is not clear yet how the drugs at first cause dendritic growth and then later prevent it. One possibility is that they affect gene expression: for instance, both new experiences and amphetamine are known to induce expression of a gene called arc, which has also been linked to changes in neurons.