A role for the circadian genes in drug addiction

Abstract

Diurnal and circadian rhythms are prominent in nearly all bodily functions. Chronic disruptions in normal sleep wake and social schedules can lead to serious health problems such as those seen in shift worker's syndrome. Moreover, genetic disruptions in normal circadian gene functions have recently been linked to a variety of psychiatric conditions including depression, bipolar disorder, seasonal affective disorder and alcoholism. Recent studies are beginning to determine how these circadian genes and rhythms are involved in the development of drug addiction. Several of these studies suggest an important role for these genes in limbic regions of the brain, outside of the central circadian pacemaker in the suprachiasmatic nucleus (SCN). This review summarizes some of the basic research into the importance of circadian genes in drug addiction.

Figure 1

Cartoon depicting the molecular clock. CLOCK and BMAL1 (or NPAS2 and BMAL1) regulate the expression of the Period and Cryptochrome genes. These are translated in the cytoplasm and are phosphorylated. They enter the nucleus and inhibit the activity of CLOCK:BMAL1. A separate loop depicted at the bottom of the nucleus shows the regulation of Bmal1 by Rorα and Rev-erbα.