“Tanning is addictive”: um, not quite

“Repeated visits to the beach or tanning salon could be signs of an addiction, according to a study in mice.” – Nature, Research highlights doi:10.1038/510447e. Image credit: etsishats.com

Summer is finally in full swing, and to many that means one thing: tanning at the beach! Despite being well aware of the serious health risks associated with UV light exposure, tanning aficionados repeatedly seek out toxic rays. Two small studies show that frequent tanners experience withdrawal symptoms when given naloxone, a drug that blocks the action of opioids like heroin. Is our love for tanning simply a reflection of western aesthetics, or is tanning actually physiologically addictive?

Off with the fur and in with the tanning salons!

Mice with clean-shaved backs received a daily dose of UV light for 42 days, at an amount roughly equal to tanning under the Florida sun in the summer at midday for 20-30min. Unbeknownst to them, some mice only went through the motions, getting mock UV treatment instead. After a week, the levels of circulating β-endorphins (an endogenous opioid involved in analgesia and addiction) increased by ~30-50% in UV-exposed mice, which remained high throughout the experiment but returned back to baseline within a week after the last tanning session (see graph below, A). In contrast, β-endorphin levels remained normal in their mock-treated peers.

A: UV exposure, with or without naloxone (circle and square) increased b-endorphine levels in the blood. Mock UV did not (triangles). B and C: UV treatment increased pain tolerance (the bump), which disappeared with naloxone treatment (grey squares). Naloxone increases sensitivity to pain (lower threshold and latency) in all mice (grey lines are lowest).

Like morphine, β-endorphins act on opioid receptors and numb pain. Researchers carefully assessed the mice’s tolerance to pain by prodding their paws with a metal wire (B above) or heat (C). Daily UV light exposure increased both pain thresholds, which correlated in time with the rise in β-endorphins. The effect disappeared if the mice were given the opioid blocker naloxone two times a week, suggesting that activated opioid receptors are behind the insensitivity to pain. As expected, pain thresholds of mock-treated mice didn’t change.

β-endorphins have another quirky action in rodents: they cause muscle contractions near the tailbone, resulting in rigid tails. Within 10 days of their first tanning session, mice perked up their tails, which lasted the duration of UV exposure. Again, a dose of naloxone relaxed the muscles, and the tails returned to their normal limp state.

In tanning mice, naloxone relaxes their perked up tails.

However, temporarily increased β-endorphins can signal many things, such as wound healing after injury. Can β-endorphins in the skin cause addiction in the brain? Researchers took a group of untreated mice and mainlined β-endorphins through their tail in a white box – an environment that rodents naturally dislike. Yet when given the option to chill in a far more appealing place (a black box), the mice refused to budge. Just like addicts returning to their usual set and setting, these mice preferred their β-endorphin den.

Chronic drug use causes tolerance not only for the specific drug-of-choice, but also for drugs with similar actions. Compared to their mock treated peers, UV-exposed mice required a higher dose of morphine to achieve the same analgesic effect despite their higher pain tolerance, suggesting that they had developed cross-tolerance to other members of the opioid family.

If β-endorphins cause physical dependence like heroin, then quitting cold turkey should induce signs of withdrawal. After receiving naloxone, UV-treated mice showed 4 out of 6 common withdrawal symptoms, including shaky paws and chattering teeth (see graph below). They also despised the place where they had received naloxone, instead voluntarily running to a terrifying, brightly lit room when given the chance while avoiding the naloxone-associated room like the plague.

A shot of naloxone triggers several withdrawal symptoms in tanning bro mice.

Finally, a little molecular sleuthing found that the increased β-endorphins come from the skin. UV exposure damages DNA, which activates a guardian protein called p53 that helps suppress tumours. When researchers specifically deleted p53 in a type of skin cells called keratinocytes, the mutant mice no longer showed elevated β-endorphin levels or increased pain tolerance after their tanning sessions.

Overall it’s a simple but elegant story. But it’s far too early to conclude that the sun is getting you high. Many of the observed effects after UV-light exposure – such as increased pain tolerance and cross-tolerance to morphine – can be explained by biological mechanisms happening in the periphery of the body (downregulation of opioid receptors in the skin, for example). A better test of cross-tolerance that directly demonstrates addiction would be to see if UV-exposed mice require higher doses of morphine or heroin to get high. That naloxone treatment precipitates withdrawal symptoms is more convincing at suggesting that the brain is involved, but it doesn’t prove addiction. Quitting heroin cold turkey causes severe withdrawal symptoms; can we say the same for quitting moderate bouts of tanning?

Addicts are willing to sacrifice anything and everything for their drug-of-choice. Drive, or motivation to seek out and obtain the drug is a key sign of addiction, and something not demonstrated in this study. Would mice be willing to work for UV light as they do for cocaine and heroin (e.g. pressing a lever to switch on the rays)? Would they venture into UV rays despite negative consequences, such as getting zapped with electrical shocks? Would they be prone to relapse after quitting their sunbathing addiction?

A common brain circuit hijacked by all drugs of abuse is the limbic reward system. Heroin, for example, increases dopamine levels in the midbrain and tweaks the synapses to promote long-lasting memories associated with the drug. Can increased β-endorphins from tanning act on these addiction-related circuits?

Fell GL, Robinson KC, Mao J, Woolf CJ, & Fisher DE (2014). Skin β-Endorphin Mediates Addiction to UV Light. Cell, 157 (7), 1527-34 PMID: 24949966