Dopamine receptors
Action of dopamine on SPNs of the dorsal striatum is mediated by two main subtypes of dopamine receptors, D1 and D2 (Meador-Woodruff, 1996). Expression of D1R and D2R is highly segregated: D1R are predominantly localized in the SPNs driving the direct pathway, while D2R are mostly presented in cells of indirect one, and only small portion of projection neurons in the dorsal striatum express both receptor subtypes (Lanciegoet al. , 2012; Gagnon et al. , 2017). Binding of dopamine with D1R which are exclusively presynaptic leads to activation of SPNs of the direct pathway and results in moderate stimulation of locomotor activity (Missale et al. , 1998; Beaulieu & Gainetdinov, 2011). D2R are expressed both in pre- and postsynapses, so that their role in the regulation of locomotion is more complicated. Thus, it is generally assumed that activation of presynaptic D2R decreases dopamine release suppressing locomotor activity, while activation of postsynaptic D2R on the striatal cells leads to inhibition of indirect pathway SPNs and, in hence, potentiates locomotion (Beaulieu & Gainetdinov, 2011).
Our data showed that neither 3-day HU nor 3-day SI affected the expression of D2R in the dorsal striatum. At the same time, D1R expression was significantly elevated in the dorsal striatum of HU mice in comparison with both SI and GH animals. These changes might as well be compensatory and reflect the adaptation of the striatum to decreased dopamine innervation under HU. Analogously, increased dopamine receptor expression and binding was demonstrated for patients with early stages of Parkinson’s disease in which extremal loss of dopamine transmission is observed (Seeman & Niznik, 1990; Kaasinen et al. , 2021). On the other hand, changes in expression of D1R along with unchanged content of D2R could indicate that D1R-linked signaling was more sensitive to the effect of HU.