Racing the clock: The role of circadian rhythmicity in addiction across the lifespan

Although potent effects of psychoactive drugs on circadian rhythms were first described over 30 years ago, research into the reciprocal relationship between the reward system and the circadian system - and the impact of this relationship on addiction - has only become a focus in the last decade. Nonetheless, great progress has been made in that short time toward understanding how drugs of abuse impact the molecular and physiological circadian clocks, as well as how disruption of normal circadian rhythm biology may contribute to addiction and ameliorate the efficacy of treatments for addiction. In particular, data have emerged demonstrating that disrupted circadian rhythms, such as those observed in shift workers and adolescents, increase susceptibility to addiction. Furthermore, circadian rhythms and addiction impact one another longitudinally - specifically from adolescence to the elderly. In this review, the current understanding of how the circadian clock interacts with substances of abuse within the context of age-dependent changes in rhythmicity, including the potential existence of a drug-sensitive clock, the correlation between chronotype and addiction vulnerability, and the importance of rhythmicity in the mesocorticolimbic dopamine system, is discussed. The primary focus is on alcohol addiction, as the preponderance of research is in this area, with references to other addictions as warranted. The implications of clock-drug interactions for the treatment of addiction will also be reviewed, and the potential of therapeutics that reset the circadian rhythm will be highlighted.