Conclusion
Results of the present study suggested that dysregulation of the dopaminergic system in the substantia nigra was mainly associated with HU, whereas in the dorsal striatum both HU and SI contributed to the attenuation of dopamine signaling. We demonstrated that HU significantly impaired activity of TH indicating a decrease in dopamine synthesis in the nigrostriatal system of mice. In turn, reduced dopamine innervation was accompanied with significant reduction in the activity of PKA and transcriptional factor CREB in the dorsal striatum that, in hence, pointed on decrease in the activity of striatal cells. At the same time SI itself only decreased TH activity in the striatum, while no changes in dopamine-related signaling was observed.
Noteworthy, HU and SI are abnormal states which can induce stress responses (Globus & Morey-Holton, 2016; Mumtaz et al. , 2018; Tahimic et al. , 2019). However, the studies suggested that, while acute stress (hours) elevated synthesis and release of the nigrostriatal dopamine, chronic stress (days) exerted no effect (Abercrombie et al. , 1989; Castro & Zigmond, 2001; Baik, 2020). Thus, the effect of HU on dopamine transmission in the nigrostriatal system observed in the present work was more likely associated with a loss of sensorimotor stimuli and partial muscle disuse, while SI-induced dysregulation could be caused mainly by a decrease in locomotor activity associated with the absence of cage-mates. Nevertheless, further investigations are needed to distinguish the effects of muscle unloading and social isolation more precisely. In addition, analysis of long-term effects of these factors on the nigrostriatal system should be performed to trace the dynamics of changes that can be associated with development of locomotor disorders.