Neural Mechanisms of Circadian Regulation of Natural and Drug Reward

Figure 1

Multiple brain regions are activated or regulated by reward. Anticipation of (a) natural rewards, namely, food and (b) drugs of abuse activate discrete circuitry. The rhythmic expression of circadian genes in this and other brain regions is also altered by food or drugs of abuse demonstrating one potential mechanism by which reward influences circadian rhythms. (a) Anticipating a scheduled meal or palatable snack activates or increases c-Fos expression in the prefrontal cortex (PFC), nucleus accumbens (NAc), central amygdala, and hypothalamus. Furthermore, palatable food alters the expression of circadian genes in these and other brain regions. Per1 rhythms are altered and shifted in the amygdala, NAc, and PFC, whereas the amplitude of Per2 rhythms are intensified in the lateral habenula [116] as well as the suprachiasmatic nucleus (SCN not shown), cortex, and striatum [117] during anticipation of chocolate or after consumption of a high fat/high sugar diet or sucrose, respectively. (b) Anticipating drugs of abuse can activate multiple brain regions including the caudate, thalamus, insula, NAc, hippocampus, ventral pallidum, and cingulate. Similar to food, drugs of abuse also alter the expression of circadian genes. Specifically, cocaine alters the rhythm of Npas2 and Drd3 as well as the expression of numerous circadian genes in the NAc, most of which are upregulated. Circadian rhythms of period genes are also altered after withdrawal from morphine in the SCN, PFC, NAc, central and basolateral amygdala, hippocampus, and ventral tegmental area (not shown). Although it is beyond the scope of this figure to examine the differences in activation and circadian gene expression in various stages of addiction, it is important to note that acute versus chronic exposure to rewards have some distinct effects on the reward circuity in the brain. For example, it is known that the role of various brain regions shifts during extended exposure to drugs of abuse (reviewed in [118]). It is thought that this shift contributes to the transition from use to abuse to dependence. Similarly, circadian genes may be contributing to this transition since mutations in these genes cause a loss of rhythmicity [16], which is also thought to contribute to loss of control over drug taking and the transition to addiction.

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