Cocaine is known to increase brain dopamine at supranormal levels in comparison to alternative nondrug rewards. According to the dopamine hypothesis of addiction, this difference would explain, at least in part, why the latter are eventually given up in favor of continued cocaine use during the transition to addiction. Though resting on solid neuroscientific foundations, this hypothesis has nevertheless proven difficult to reconcile with research on cocaine choice in experimental animals. When facing a choice between an intravenous bolus of cocaine and a nondrug alternative (e.g., sweet water), both delivered immediately after choice, rats do not choose the drug, as would be predicted, but instead develop a strong preference for the nondrug alternative, sometimes to the exclusion of continued drug use. Here we report converging evidence that reconciles this finding with the dopamine hypothesis of addiction. Briefly, our data suggest that cocaine is indeed supranormal in reward magnitude, as postulated by the dopamine hypothesis of addiction, but is less preferred during choice because its pharmacokinetics makes it an inherently more delayed reward than the alternative. Reframing previous drug choice studies in rats as intertemporal choice studies reveals that the discounting effects of delays spare no rewards, including supranormal ones, and that during choice, pharmacokinetics trumps pharmacodynamics. Finally, this study also reveals important gaps in our understanding of drug reward delays that need to be filled by future experimental and theoretical work.

Cocaine is known to increase brain dopamine at supranormal levels in comparison to alternative nondrug rewards. According to the dopamine hypothesis of addiction, this abnormally large dopamine response would explain why cocaine use is initially highly rewarding and addictive. Though resting on solid neuroscientific foundations, this hypothesis has nevertheless proven difficult to reconcile with research on cocaine choice in experimental animals. When facing a choice between an intravenous bolus of cocaine and a nondrug alternative (e.g., sweet water), both delivered immediately after choice, rats do not choose the drug, as would be predicted, but instead develop a strong preference for the nondrug alternative. Here we report evidence that reconciles this finding with the dopamine hypothesis of addiction. First, a systematic literature analysis revealed that the delays of effects of intravenous cocaine on nucleus accumbens dopamine are of the order of tens of seconds and are considerably longer than those of nondrug reward. Second, this was confirmed by measuring response times to cocaine omission during self-administration as a behavioral proxy of these delays. Finally, when the influence of the drug delays was reduced during choice by adding an increasing delay to both the drug and nondrug rewards, rats shifted their choice to cocaine. Overall, this study suggests that cocaine is indeed supranormal in reward magnitude, as postulated by the dopamine hypothesis of addiction, but is less preferred during choice because its pharmacokinetics makes it an inherently more delayed reward than the alternative. Reframing previous drug choice studies in rats as intertemporal choice studies reveals that the discounting effects of delays spare no rewards, including supranormal ones, and that during choice, pharmacokinetics trumps pharmacodynamics.

Skin wounds are common and represent a major public health and economical problem, with risks of complications and a significant negative impact on the quality of life of patients. Cutaneous wound healing is a tightly regulated process resulting in the restoration of tissue integrity. Wound healing involves the interaction of several skin, immune and vascular cells, growth factors and cytokines. However, external actors can play an important role in wound healing, such as the skin microbiome, which is the microbial commensal collection of bacteria, fungi and viruses inhabiting the skin. Indeed, recent advances have featured the interactions, within the wound environment, between different microbial species and between microbial species and the host immune system. This article reviews the relationship between the skin microbiome and the wound healing process. Although cutaneous wounds are a potential entry site for infection, the wound microbiome can have either a detrimental or a beneficial role on wound healing. Thus, targeting the skin microbiome could represent an essential part of wound healing management.

A thorough knowledge of non‐surgical procedures (laser, peelings, injections, threads) and surgical procedures (combined surgeries and skin grafts), including contraindications and potential risks and side effects, (e.g. infection, hypopigmentation, hyperpigmentation, and scarring) is essential to be able to reduce their incidence and ensure the patient receives the most benefit from the procedure. Individuals with darker skin and of high Fitzpatrick phototype are at higher risk of dyschromias, notably melasma and post‐inflammatory hyperpigmentation, which may be treated using aesthetic procedures but may also arise as a complication of some procedures. A group of experts in cosmetic surgery and dermatology reviewed the published literature and discussed recommendations for optimizing outcomes with practical advice on supportive skincare before, during and after non‐surgical or surgical procedures. A broad‐spectrum sunscreen with a high sun protection factor against UVB and high protection against UVA, especially long UVA, is essential for all treatment modalities for the prevention and potential improvement of pigmentation disorders. Supportive skin care management to prepare, cleanse and protect the skin and post‐procedure skin care with healing and anti‐inflammatory ingredients are recommended to speed up regeneration and wound healing whilst minimizing scarring and downtime. Additionally, adjunctive skin care to procedures with antioxidant, anti‐ageing and lightening properties may enhance skin benefits.