The circadian system controls the timing of physiological processes in the body. The internal period is ensured by feedback loops of clock genes, but the smooth functioning of the circadian system depends on synchronization with the light cycle. Ketamine is an antagonist of NMDA receptors and is used as a safe anesthetic for children and as an antidepressant with rapid onset of action. Previous experiments have shown that a high, anaesthetic dose causes phase shifts in circadian rhythms and disrupts photic entrainment. Based on the differential effects of a low dose of ketamine on the excitability of brain structures, we hypothesize that ketamine at low doses may prolong its antidepressant effects through its effects on the circadian system. In the proposed project, we will investigate the effects of ketamine on circadian rhythms of locomotor activity and clock genes expression. In addition, we will test the effect of ketamine on the magnitude and direction of phase shifts of circadian rhythms following a light pulse and on the level of light-induced transcription factors in the SCN. The extent of induction of well-defined markers of synaptogenesis and neurogenesis will be compared in the cortical layers, hippocampus, and progenitor regions of the brain, as well as in the SCN following ketamine application during active and resting phases in a rat.
Five relevant publications of the research group:
- Circadian control of kynurenine pathway enzymes in the rat pineal gland, liver, and heart and tissue- and enzyme-specific responses to lipopolysaccharide. Moravcová S, Spišská V, Pačesová D, Hrubcová L, Kubištová A, Novotný J, Bendová Z. Arch Biochem Biophys. 2022 Jun 15;722:109213. doi: 10.1016/j.abb.2022.109213.
- Constant Light in Critical Postnatal Days Affects Circadian Rhythms in Locomotion and Gene Expression in the Suprachiasmatic Nucleus, Retina, and Pineal Gland Later in Life. Kubištová A, Spišská V, Petrželková L, Hrubcová L, Moravcová S, Maierová L, Bendová Z. Biomedicines. 2020 Dec 7;8(12):579. doi: 10.3390/biomedicines8120579.
- Neonatal Clonazepam Administration Induced Long-Lasting Changes in GABAA and GABAB Receptors. Kubová H, Bendová Z, Moravcová S, Pačesová D, Rocha L, Mareš P. Int J Mol Sci. 2020 Apr 30;21(9):3184. doi: 10.3390/ijms21093184.
- The day-night differences in ERK1/2, GSK3β activity and c-Fos levels in the brain, and the responsiveness of various brain structures to morphine. Bendová Z, Pačesová D, Novotný J. J Comp Neurol. 2020 Oct;528(14):2471-2495. doi: 10.1002/cne.24906.
- The effect of the cannabinoid receptor agonist and antagonist on the light-induced changes in the suprachiasmatic nucleus of rats. Filipovská E, Červená K, Moravcová S, Novotný J, Kyclerová H, Spišská V, Pačesová D, Bendová Z. Neurosci Lett. 2019 Jun 11;703:49-52. doi: 10.1016/j.neulet.2019.03.022.
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