title: Skin β-endorphin mediates addiction to UV light.
abstract: UV light is an established carcinogen, yet evidence suggests that UV-seeking behavior has addictive features. Following UV exposure, epidermal keratinocytes synthesize proopiomelanocortin (POMC) that is processed to melanocyte-stimulating hormone, inducing tanning. We show that, in rodents, another POMC-derived peptide, β-endorphin, is coordinately synthesized in skin, elevating plasma levels after low-dose UV. Increases in pain-related thresholds are observed and reversed by pharmacologic opioid antagonism. Opioid blockade also elicits withdrawal signs after chronic UV exposure. This effect was sufficient to guide operant behavioral choices to avoidance of opioid withdrawal (conditioned place aversion). These UV-induced nociceptive and behavioral effects were absent in β-endorphin knockout mice and in mice lacking p53-mediated POMC induction in epidermal keratinocytes. Although primordial UV addiction, mediated by the hedonic action of β-endorphin and anhedonic effects of withdrawal, may theoretically have enhanced evolutionary vitamin D biosynthesis, it now may contribute to the relentless rise in skin cancer incidence in humans.
authors.affiliation: Cutaneous Biology Research Center, Department of Dermatology and MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Gillian L
authors.initials: GL
authors.lastname: Fell
authors.affiliation: Cutaneous Biology Research Center, Department of Dermatology and MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Robinson
authors.affiliation: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Jianren
authors.initials: J
authors.lastname: Mao
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02114, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Woolf
authors.affiliation: Cutaneous Biology Research Center, Department of Dermatology and MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: dfisher3@partners.org.
authors.forename: David E
authors.initials: DE
authors.lastname: Fisher
mesh_terms: D000818:Animals; D016739:Behavior, Addictive; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays; D001615:beta-Endorphin / Q000235:genetics / Q000378:metabolism*
chemical_list: D001615:beta-Endorphin