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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F19%3A00503786" target="_blank" >RIV/61389030:_____/19:00503786 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/19:10396970

Result on the web

<a href="http://doi.org/10.3389/fphar.2019.00237" target="_blank" >http://doi.org/10.3389/fphar.2019.00237</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2019.00237" target="_blank" >10.3389/fphar.2019.00237</a>

Result language

angličtina

Original language name

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

Original language description

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

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30210 - Clinical neurology

Project

<a href="/en/project/GA17-03847S" target="_blank" >GA17-03847S: The role of M4 muscarinic receptors in biorhythm regulation</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Pharmacology

ISSN

1663-9812

e-ISSN

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Volume of the periodical

10

Issue of the periodical within the volume

MAR 18

Country of publishing house

CH - SWITZERLAND

Number of pages

11

Pages from-to

237

UT code for WoS article

000461674000001

EID of the result in the Scopus database

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