Zebrafish Will Risk Their Lives For Drug Hit

From the look of them, you wouldn't know these fish are desperate for their next opioid hit. Univeristy of Utah Health

To understand addiction, neuroscientists have given drugs to rats, but a new study shows zebrafish like opioids too, providing an alternative path for future research.

Dr Gabriel Bossé of the University of Utah gave zebrafish the opportunity to self-administer hydrocodone, an opioid prescribed as a pain reliever that frequently becomes a drug of addiction. Within a week, the fish were willing to journey into danger for a hit, and showed signs of anxiety when their supply was cut off.

"Drugs of abuse target the pathways of the pleasure centers very effectively," said Bossé in a statement. "These pathways are conserved in zebrafish, and the fish can experience some of the same signs of addiction and withdrawal as people."

The fish in the experiment were taught to trigger the release of food by swimming over a platform. A matching platform had no effect, and the fish quickly learned to spend more time crossing the active platform. In a second experiment reported in Behavioral Brain Research, activating the platform led to the release of hydrocodone into the water supply, administering the drug to the fish.

Treating the addicted zebrafish with naloxone, an opioid-receptor blocker, as well as dopamine and glutamate blockers, reduced drug-seeking behavior.

“We didn't know if zebrafish would be a relevant model for opioid addiction, much less self-administer the drug," said co-author Professor Randall Peterson. Fish are a cheaper model than rats or primates, so they may allow researchers to test a wider array of treatment options, with the most promising choices subsequently tried on more human-like animals. Zebrafish are also easy to modify genetically, enabling tests of which genes encourage drug-administration.

Nevertheless, this is a field where extrapolation from animals can mislead. Early research found rats become easily hooked on drugs such as cocaine and heroin, and the work was used to make the case that these drugs were universally addictive. However, other researchers noted that the lab rats were kept isolated and with nothing to do. When rats, a communal species, are kept with others or in a stimulating environment, only about 10 percent become addicted, no matter how large the drug doses they are given.

Moreover, researchers in the field consider a range of behaviors markers of addiction, beyond simply self-administration. A rat that self-administered a drug, but didn't prefer it to food or sex might not be considered addicted, so the status of these fish is unclear.

Opioids are not always recreational for fish. Fang blennies, a type of small reef fish, have been shown to use opioids in their venom to disorientate predators. On the other hand, goldfish make their own alcohol, so maybe it's not so surprising fish have an affinity for drugs that humans like.

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