Abstract
A number of studies implicate biogenic amines in regulating circadian rhythms. In particular, dopamine and serotonin influence the entrainment of circadian rhythms to daily food availability. To study circadian entrainment to feeding, food availability is typically restricted to a short period within the light cycle daily. This results in a notable increase in pre-meal activity, termed “food anticipatory activity” (FAA), which typically develops within about 1 week of scheduled feeding. Several studies have implicated serotonin as a negative regulator of FAA: (1) aged rats treated with serotonin 5-HT2 and 3 receptor antagonists showed enhanced FAA, (2) mice lacking for the 2C serotonin receptor demonstrate enhanced FAA, and (3) pharmacologically increased serotonin levels suppressed FAA while decreased serotonin levels enhanced FAA in mice. We sought to confirm and extend these findings using genetic models with impairments in central serotonin production or re-uptake, but were surprised to find that both serotonin transporter (Slc6a4) and tryptophan hydroxylase-2 knockout mice demonstrated a normal behavioral response to timed, calorie restricted feeding. Our data suggest that FAA is largely independent of central serotonin and/or serotonin reuptake and that serotonin may not be a robust negative regulator of FAA.
Highlights
Biological rhythms influence most cellular, physiological, and behavioral processes: from metabolic rate (Oklejewicz et al, 1997) to cancer stem cell proliferation (Puram et al, 2016), xenobiotic metabolism (DeBruyne et al, 2014), and glucose homeostasis (Versteeg et al, 2015)
Once mice have been maintained on a feeding schedule for about 1 week they will develop food anticipatory activity (FAA), which is a marked increase in arousal and physical activity in the 2– 3 h preceding scheduled mealtime (Mistlberger, 2011)
The only area of consistent agreement is that the suprachiasmatic nucleus (SCN) is not required for FAA (Davidson, 2009), it might modulate the amplitude of food rhythms (Acosta-Galvan et al, 2011)
Summary
Biological rhythms influence most cellular, physiological, and behavioral processes: from metabolic rate (Oklejewicz et al, 1997) to cancer stem cell proliferation (Puram et al, 2016), xenobiotic metabolism (DeBruyne et al, 2014), and glucose homeostasis (Versteeg et al, 2015). Much is known about how light influences circadian rhythms of mammals by regulating the activity of neurons in the suprachiasmatic nucleus (SCN) (Mohawk et al, 2012). Food Entrainment Independent of Serotonin a molecular clock, orchestrating the release of hormones and other physiological processes regulated by the hypothalamus (Welsh et al, 2010). Comparatively little is known about how other environmental cues, such as feeding, tune circadian rhythms (Steele and Mistlberger, 2015). The underlying neuronal systems and/or circuitry responsible for mediating FAA are hotly contested, with very few studies showing reproducible effects of mutations or lesions (Davidson, 2009; Gunapala et al, 2011; Pendergast and Yamazaki, 2018). The only area of consistent agreement is that the SCN is not required for FAA (Davidson, 2009), it might modulate the amplitude of food rhythms (Acosta-Galvan et al, 2011)
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