Melatonin and the Chronobiology of Drug Abuse

Drug dependence is a multifactorial behavioral and biological disorder. Its current treatment involves psychosocial and pharmacological interventions. The major aims of these interventions are (i) reduction of drug use and craving; (ii) improvement of general well-being of the individual; and (iii) prevention of the risk of the development of comorbidities and/or recurrence. These objectives, however, are far from being achieved and current available treatment options remain inadequate, with varying addiction relapse rates, depending on the drugs involved. In this chapter, I will analyze the potential use of melatonin to ameliorate different aspects of addiction in experimental animal models and humans. Experimental findings indicate that exogenous melatonin supplementation or therapeutic manipulation of melatonin/melatonin receptor interactions can be beneficial in the management of behavioral manifestations of drug abuse. Studies in brain areas associated with reward and emotionality have revealed the efficacy of melatonin supplementation in the control of drug-seeking behavior, behavioral sensitization, neuroplasticity, and prevention of mitochondrial-induced autophagy, apoptosis, oxidative stress, and neurotoxic injury. Interaction between the circadian system and drug addiction exists, clock gene expression being altered during the development of drug addiction in many brain areas related to drug reward. Melatonin use in addict individuals can be a successful chronobiological strategy aimed at restoring/stabilizing circadian rhythms to reduce the risk for addiction development and relapse.