Drugs of abuse and the science behind addiction remain poorly understood. Researchers at University of Utah Health devised a system that allowed zebrafish, a small tropical fish, to self-administer doses of hydrocodone, an opioid commonly prescribed to people for pain. After one-week, the fish had increased their drug-seeking behavior, even when doing so required them to put themselves in risky conditions. Further, 48-hours after the last exposure, conditioned fish showed signs of anxiety, a hallmark of withdrawal. Zebrafish share 70 percent of genes with people and also share similar biological pathways that lead to addiction. Drug-seeking behavior also increased when the zebrafish were forced to receive the opioid in progressively shallower water, a stressful environmental setting that unconditioned fish would avoid. Further, fish that received a reduced dose of hydrocodone at the original depth increased their drug-seeking behavior to obtain an equivalent “fix.” Conditioned zebrafish treated with naloxone, a drug that blocks the m-opioid receptor, as well as dopamine- or glutamate-blockers reduced their drug-seeking behavior during the experiments. The researchers plan to use their zebrafish model to search for new therapeutics that could block drug-seeking behavior.