Rubbing against catnip and silver vine transfers plant chemicals that researchers have now shown protect cats from mosquitoes. The results also demonstrate that engaging with nepetalactol, which the study identified as the most potent of many intoxicating iridoid compounds found in silver vine, activates the opioid reward system in both domesticated felines and big jungle cats. While nepetalactol had been previously identified, these studies directly illuminate its extremely potent effect on cats. And by revealing the biological significance of well-known feline behaviors, the study opens the door to further inquiry into how nepetalactol's twin effects - pest repellence and intoxication - may have driven the evolution of these behaviors. Catnip and silver vine are known to hold a special place in felines' hearts. When cats encounter these plants, they rub their heads and faces against them and roll around on the ground, displaying undeniable enjoyment. Afterward, the cats lounge around in a state of intoxicated repose. But while pet owners around the world gift their cats toys laced with catnip or silver vine leaves, the biological significance of these plants and the neurophysiological mechanism triggered when cats sniff and rub against them has not been known. To investigate, Reiko Uenoyama and colleagues tested how 25 laboratory cats, 30 feral cats, and several captive big cats, including an Amur leopard, two jaguars, and two Eurasian lynx, responded to filter paper impregnated with nepetalactol, finding that the cats showed a more prolonged response than they did with untreated control filter papers. In contrast, dogs and laboratory mice showed no interest in the nepetalactol-containing papers. Next, the researchers compared how 12 of the cats responded to each of the known bioactive iridoids, finding that nepetalactol is the most potent compound in silver vine leaves. To test whether feline responses to nepetalactol are regulated by the opioid system, they examined changes in plasma levels of ?-endorphin 5 minutes before and 5 minutes after 5 cats were exposed to nepetalactol, and later to a control stimulus, finding elevated endorphin concentrations only after exposure to the iridoid. When the researchers pharmacologically inhibited the cats' ?-opioid receptors, the cats no longer showed a rubbing response to the iridoid. Finally, they tested whether silver vine leaves repelled Aedes albopictus mosquitoes when cats rubbed against the plant, finding that significantly fewer mosquitoes landed on cats that exhibited this behavior. Uenoyama et al. note that nepetalactol might also be used as a repellent to protect humans from mosquitoes and suggest it could also repel the Aedes aegypti species, which transmits yellow fever, dengue, and Zika viruses.