The Sunny Side of Addiction

Sci. Signal.  01 Jul 2014:
Vol. 7, Issue 332, pp. ec178
DOI: 10.1126/scisignal.2005640

Humans seek sun exposure despite awareness of potentially deleterious effects, such as skin cancer. Exposure to ultraviolet light (UV) induces DNA damage in keratinocytes that activates p53-dependent transcription of proopiomelanocortin (POMC), which is translated and cleaved to produce peptides, including the pigment-inducing hormone α-MSH and the endogenous opioid β-endorphin. Fell et al. found that skin-derived β-endorphin caused UV addiction. Dorsally shorn mice exposed to a daily, moderate amount of UV had increased circulating concentrations of β-endorphin, which led to muscular contraction and increased pain thresholds in response to mechanical and thermal stimuli, consistent with systemic activation of μ-type opioid receptors. Cessation of UV exposure or acute administration of the opioid receptor antagonist naloxone reversed these effects. Acute naloxone administration to UV-exposed mice caused withdrawal symptoms similar to those observed in opioid-dependent mice. UV exposure induced cross-tolerance to the pain-reducing effects of the exogenous opioid morphine. UV exposure did not increase circulating β-endorphin in mice with keratinocyte-specific deletion of the gene encoding p53 (TP53). Moreover, keratinocyte-specific deletion of TP53 or global deletion of the region of the POMC gene encoding β-endorphin prevented UV exposure-induced increases in pain threshold and the behavioral manifestations of opioid dependence. Thus, exposure to sunlight or artificial light in UV tanning beds induces β-endorphin release by skin cells that causes a central neurological response associated with positive reinforcement and addictive behavior (see Tejeda and Bonci).

G. L. Fell, K. C. Robinson, J. Mao, C. J. Woolf, D. E. Fisher. Skin β-endorphin mediates addiction to UV light. Cell 157, 1527–1534 (2014). [PubMed]

H. A. Tejeda, A. Bonci, Shedding “UV” light on endogenous opioid dependence. Cell 157, 1500–1501 (2014). [PubMed]