Monoamine receptors of intrinsic spinal neurons and their role in mammalian locomotor control: from physiology to pathology.

Abstract

Locomotor impairment is one of the most devastating consequences of spinal cord injury (SCI) and cannot be adequately overcome by existing rehabilitation methods. Numerous studies in spinalized mammals have demonstrated that serotonin, dopamine, and noradrenaline receptors located on spinal cord cells below the injury level play an important role in locomotor recovery. Hence, these monoamine receptors (MARs) represent promising targets for pharmacological rehabilitation following SCI, but no drug targeting them has yet proven sufficiently effective for locomotor recovery or reached clinical use. This review summarizes current data on the spinal localization of MARs, their postinjury changes (expression and function), and the role of specific receptor subtypes and their combinations in regulating kinematic, kinetic, and electromyographic locomotor parameters in intact and spinalized mammals. Specifically, the studies reviewed here show that some MARs are important for locomotor control in healthy animals, while the role of others becomes apparent only after SCI. Data on changes in receptor expression following SCI are contradictory and strongly depend on the experimental protocol, animal species, and sex, as well as on the type of sample analyzed. Finally, targeting different receptor subtypes affects distinct locomotor parameters, whereas simultaneous targeting of multiple receptors (e.g., 5-HT1AR + 5-HT2A/2CR + D1R + α2AR) can produce a synergistic effect. Therefore, the development of highly selective drugs and knowledge of post-traumatic changes occurring in receptors will enable targeting of a narrow spectrum of receptors and correction of individual locomotor parameters depending on the degree of their impairment.