The differential effects of dopamine d2, d3 agonist, quinpirole on circadian rest-activity rhythm according to dosing time
Year: 2022
Type: article
Abstract: Introduction: Previous animal studies showed D2, D3 receptor agonist quinpirole might increase locomotor activity administered in dark phase which is the daytime for human.However, there is a lack of study on the effects of quinpirole administrated during light phase.Given that the release of dopamine is regulated by circadian clock, dopaminergic agents administrated at light phase misaligned with circadian dopamine rhythms could have different effects compared to dark phase.Therefore, it would be important to investigate the differential effects of D2, D3 receptor agonist quinpirole according to dosing time and understand the role of dopaminergic agents as a circadian modulator.Aims: We aimed to compare the effect of repeated administrated quinpiroles on circadian rest-activity in dark phase or light phase, respectively.Methods: The locomotor activities of ten male Institute Cancer Research (ICR) mice were measured by infrared motion detectors in home cages.To compare the effect of quinpirole administrated in light phase and dark phase, 0.5mg/kg of quinpirole was administrated intraperitoneally at 9 a.m. and 5 p.m., and the light of the home cage was automatically controlled by a lighting system at 12-hour intervals.The circadian rest-activity rhythms were estimated by the summation for every 12 hours and 24 hours, Also cosine analysis done by Matlab R2021b (MathWorks, Natick, MA, USA).Then the data were analysed by nonparametric analysis and Repeated Measure Analysis of Variance using Statistical Package for Social Sciences version 23.0 (SPSS Inc., Chicago, IL, USA) Summary of Results: After quinpirole administrations in dark phase, the locomotor activities in the dark phase were significantly increased compared to the baseline locomotor activities (t¼-6.968,p¼0.000).The difference 12-hour darklight analysis was increased (t¼-5.335,p¼0.000), while the ratio did not (t¼1.457p¼0.179).The amplitude, MESOR, acrophase in cosinor analysis (t¼-3.442,-6.968, -4.416, p¼0.007, 0.000, 0.002, respectively), and M10, L5 and RA in non-parametric analysis were also changed significantly after the quinpirole administration (t¼-6.216,-4.100, 2.990, p¼0.000, 0.003, 0.015, respectively).In the light phase injection, there was no significant change in the locomotor activities in both dark and light phases (t¼1.574,p¼0.150).The difference and ratio of dark-light phases in 12-hour sum did not change significantly after the injection (t¼0.001,-0.529, p¼0.999, 0.609, respectively).Amplitude and acrophase showed a significant change (t¼4.531,2,788, p¼0.001, 0.021, respectively), but MESOR did not change (t¼1.754,p¼0.150).There were significant changes in M10 (t¼3.790,p¼0.004), but not in L5 and RA (t¼-1.995,2.173, p¼0.077, 0.058, respectively).Conclusion: This study suggests that when quinpirole is administrated in dark phase, it might enhance the circadian rest-activity rhythms in dark phase.In contrast, when quinpirole is given in light phase, the augmented rest-activity rhythms tend to show the disruption of the circadian rest-activity rhythm.Therefore, quinpirole may show the differential effects of circadian-rest activity rhythms according to administrating timing.Dopamine D2, D3 agonist dosing time might have crucial influences on the regulation of circadian rest-activity rhythm.
Source: Neuroscience Applied
Institutions: Pusan National University Hospital, Pusan National University
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,000
OpenAlex ID: W4313200951