Variability in the Drug Response of M-4 Muscarinic Receptor Knockout Mice During Day and Night Time

0503786 - ÚEB 2020 RIV CH eng J - Journal Article
Valuskova, P. - Riljak, V. - Forczek, Sándor - Farar, V. - Mysliveček, J.
Variability in the Drug Response of M-4 Muscarinic Receptor Knockout Mice During Day and Night Time.
Frontiers in Pharmacology. Roč. 10, MAR 18 (2019), č. článku 237. ISSN 1663-9812. E-ISSN 1663-9812
Institutional support: RVO:61389030
Keywords : dopamine transporter * suprachiasmatic nucleus * locomotor stimulation * cocaine * insights * brain * M-4 muscarinic receptor * biorhythm * motor activity * temperature * scopolamine * oxotremorine * cocaine * open field
OECD category: Clinical neurology
Impact factor: 4.225, year: 2019
Method of publishing: Open access
http://doi.org/10.3389/fphar.2019.00237

Mice are nocturnal animals. Surprisingly, the majority of physiological/pharmacological studies are performed in the morning, i.e., in the non-active phase of their diurnal cycle. We have shown recently that female (not male) mice lacking the M-4 muscarinic receptors (MR, M4KO) did not differ substantially in locomotor activity from their wild-type counterparts (C57BI/6Tac) during the inactive period. Increased locomotion has been shown in the active phase of their diurnal cycle. We compared the effects of scopolamine, oxotremorine, and cocaine on locomotor response, hypothermia and spontaneous behavior in the open field arena in the morning (9:00 AM) and in the evening (9:00 PM) in WT and in C57BV6NTac mice lacking the M-4 MR. Furthermore, we also studied morning vs. evening densities of muscarinic, GABA(A), D-1-like, D-2-like, NMDA and kainate receptors using autoradiography in the motor, somatosensory and visual cortex and in the striatum, thalamus, hippocampus, pons, and medulla oblongata. At 9:00 AM, scopolamine induced an increase in motor activity in WT and in M4KO, yet no significant increase was observed at 9:00 PM. Oxotremorine induced hypothermic effects in both WT and M4KO. Hypothermic effects were more evident in WT than in M4KO. Hypothermia in both cases was more pronounced at 9:00 AM than at 9:00 PM. Cocaine increased motor activity when compared to saline. There was no difference in behavior in the open field between WT and M4KO when tested at 9:00 AM, however, at 9:00 PM, activity of M4KO was doubled in comparison to that of WT. Both WT and KO animals spent less time climbing in their active phase. Autoradiography revealed no significant morning vs. evening difference. Altogether, our results indicate the necessity of comparing morning vs. evening drug effects
Permanent Link: http://hdl.handle.net/11104/0295562