Influence of circadian disruption on neurotransmitter levels, physiological indexes, and behaviour in rats

Abstract

Brain monoamines - such as noradrenaline (NA), dopamine (DA) and serotonin (5-HT) - regulate several important physiological functions, including the circadian rhythm. The purpose of this study was to examine changes in NA, DA and 5-HT levels in various brain regions and their effect on core body temperature (Tc), heart rate (HR) and locomotor activity (Act) in rats following exposure to an artificial light/dark (LD) cycle. For this, male Wistar rats were housed at an ambient temperature (Ta) of 23 °C and 50% relative humidity with free access to food and water. Rats were exposed to either natural (12 h:12 h) or artificial (6 h:6 h) LD cycles for 1 month, after which each brain region was immediately extracted and homogenized to quantify the amounts of NA, DA and 5-HT by high-performance liquid chromatography. Behavioural changes were also monitored by the ambulatory activity test (AAT). Notably, we found that artificial LD cycles disrupted the physiological circadian rhythms of Tc, HR and Act. Although the 5-HT levels of rats with a disrupted circadian rhythm decreased in cell bodies (dorsal and median raphe nuclei) and projection areas (frontal cortex, caudate putamen, preoptic area and suprachiasmatic nucleus) relative to the control group, NA levels increased both in the cell body (locus coeruleus) and projection area (paraventricular hypothalamus). No significant changes were found with respect to DA. Moreover, circadian rhythm-disrupted rats also showed anxious behaviours in AAT. Collectively, the results of this study suggest that the serotonergic and noradrenergic systems, but not the dopaminergic system, are affected by artificial LD cycles in brain regions that control several neural and physiological functions, including the regulation of physiological circadian rhythms, stress responses and behaviour.

A rotating light cycle promotes weight gain and hepatic lipid storage in mice

“…Diurnal rhythm in locomotor activity, observed in mice exposed to a NL cycle, were also disrupted in the RL mice irrespective of diet. This is consistent with previous studies demonstrating disruption in rodent locomotor activity in various disrupted light cycle models (36,42). Diurnal rhythm in locomotor activity is another strong driver of metabolic processes (40); therefore, disruption of this ZT could have con-tributed to the observed disruption in circadian rhythmicity of hepatic metabolic and circadian markers.…”

Are Owls and Larks Different When it Comes to Aggression? Genetics, Neurobiology, and Behavior

“…In terms of neurotransmission, Bedrosian and Nelson (2017) suggest that as Maoa expression is oscillatory and regulated by clock genes, it is likely that environmental circadian rhythm disruption affects monoamine neurotransmitters. With this in mind, in rodents, depending on the experimental lighting schedule, 5-HT, DA, and BDNF can all be affected by environmental circadian rhythm disruption paradigms (Shieh et al, 1997;Matsumura et al, 2015;Ikeno and Yan, 2016). As mentioned previously, these neurotransmitter systems are involved in the modulation of aggressive behavior.…”

Clinical Advances of Recent Discoveries about the Interaction between Circadian and Serotoninergic Systems

“…Nevertheless, the levels of 5-HT also exhibit circadian rhythmicity in several brain regions, including SCN, Pineal gland, raphe nuclei and corpus striatum (Barassin et al 2002;Versteeg, Serlie, Kalsbeek, & Fleur, 2015). In experiments on mice, the disturbance of the circadian rhythm led to decrease in 5-HT expression in cell bodies (the dorsal and medial raphe nuclei) and projection areas (frontal cortex, caudate putamen, preoptic area and SCN), demonstrating a clear synergism between systems, which can contribute to the understanding of disorders (Matsumura et al 2015).…”

“…As demonstrated by genetic, physiological and clinical evidence, the 5-HT and circadian system of the brain are connected to each other and converge to regulate affective behavior and pathologies (Ciarleglio, Resuehr, & McMahon, 2011). The study of the association between these two important systems becomes even more important when observed ever-increasing rates of use of SSRIs and other drugs classes of serotonergic influence by population (Matsumura et al 2015), in addition to the increasing prevalence of circadian disorders, especially linked to sleep problems (Gooley, 2016).…”

“…The circadian rhythm is regulated by various brain regions, particularly mediated through 5-HT, which can be evidenced by the large number of 5-HT receptors such as the types 1A, 1B, 2A, 2C, 5A and 7 subtypes in SCN (Smith et al 2015). Therefore, in different animal models, healthy volunteers and in patients with circadian dysfunctions, it is remarkable the importance of serotonergic neuromodulation in the maintenance of endogenous rhythms, and also in understanding how circadian dysfunction can influence the efficacy and function of the serotonergic neurotransmission (Matsumura et al 2015;Holst, Valomon, & Landolt, 2016).…”