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Zebrafish willingly dose themselves with opioid drugs, discover scientists

'Fish can experience some of the same signs of addiction and withdrawal as people'

Ian Johnston
Science Correspondent
Friday 25 August 2017 19:19 BST
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Zebrafish willingly dose themselves with opioid drugs, discover scientists

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Zebrafish appear to be as keen on opioid drugs as humans, according to a study that could help scientists discover new ways to treat addiction.

Scientists at Utah University trained the fish to swim over a yellow platform to trigger the release of some food. When this happened a green light was also set off.

They then replaced the food with hydrocodone and discovered through a number of tests that the zebrafish were very keen on the opioid painkiller.

They swam over the platform when it released the drug much more often than when it produced food.

When the dose was reduced, they increased the number of visits to compensate.

Normally zebrafish will avoid water that is too shallow, but when the drug was on offer they disregarded their normal caution when the researchers reduced the level in the tank.

The fish also showed signs of anxiety – a sign of withdrawal in humans – when they had gone 48 hours without a hit.

Dr Gabriel Bossé, one of the researchers, said: “Drugs of abuse target the pathways of the pleasure centres very effectively.

“These pathways are conserved in zebrafish, and the fish can experience some of the same signs of addiction and withdrawal as people.”

They hope to use the zebrafish to develop new drugs that can block drug-seeking behaviour by setting up large numbers of tanks to screen thousands of potential candidates.

The fish’s genes could also be altered to investigate biological pathways in the brain associated with addiction.

Professor Randall Peterson, who also took part in the study, said: “We didn’t know if zebrafish would be a relevant model for opioid addiction, much less self-administer the drug.

“What is exciting about this work is that we see many of the hallmarks of addiction in zebrafish. This could be a useful and powerful model.”

In the tests, the fish were able to self-administer the drug for 50 minutes a day over the course of five days.

The tank was flushed with water to prevent the drug from building up, forcing the fish to keep swimming over the platform to trigger more.

The fish’s reaction when the dose delivered on each occasion was reduced was also key.

“We forced the fish to do more work to receive the drug, and they were more than willing to do more work,” Professor Peterson said.

Treating the zebrafish with naloxone, a drug that blocks the opioid receptor in the brain, and other blockers reduced their drug-seeking behaviour.

Similar treatments are available for human addicts, along with substitutes like methadone, a slow-acting opioid, and buprenorphine, which produces a partial response, but there are high rates of relapse.

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