The Intersection of Central Dopamine System and Stroke: Potential Avenues Aiming at Enhancement of Motor Recovery

Annette Gower, Mario Tiberi, Annette Gower, Mario Tiberi

Abstract

Dopamine, a major neurotransmitter, plays a role in a wide range of brain sensorimotor functions. Parkinson's disease and schizophrenia are two major human neuropsychiatric disorders typically associated with dysfunctional dopamine activity levels, which can be alleviated through the druggability of the dopaminergic systems. Meanwhile, several studies suggest that optimal brain dopamine activity levels are also significantly impacted in other serious neurological conditions, notably stroke, but this has yet to be fully appreciated at both basic and clinical research levels. This is of utmost importance as there is a need for better treatments to improve recovery from stroke. Here, we discuss the state of knowledge regarding the modulation of dopaminergic systems following stroke, and the use of dopamine boosting therapies in animal stroke models to improve stroke recovery. Indeed, studies in animals and humans show stroke leads to changes in dopamine functioning. Moreover, evidence from animal stroke models suggests stimulation of dopamine receptors may be a promising therapeutic approach for enhancing motor recovery from stroke. With respect to the latter, we discuss the evidence for several possible receptor-linked mechanisms by which improved motor recovery may be mediated. One avenue of particular promise is the subtype-selective stimulation of dopamine receptors in conjunction with physical therapy. However, results from clinical trials so far have been more mixed due to a number of potential reasons including, targeting of the wrong patient populations and use of drugs which modulate a wide array of receptors. Notwithstanding these issues, it is hoped that future research endeavors will assist in the development of more refined dopaminergic therapeutic approaches to enhance stroke recovery.

Keywords: L-DOPA; amphetamine; animal stroke models; clinical trials; dopamine receptors; motor recovery; pharmacotherapy; stroke recovery.

Figures

Figure 1
Figure 1
Concept map of the potential mechanisms of action for DA-enhancing pharmacotherapies in poststroke recovery. Mechanisms of actions and effects evoked by DA-enhancing drugs, which are likely to be primarily mediated through D1- and D2-class receptors, are depicted in colored boxes. The DA-enhancing actions culminating in astrocytic-dependent regulatory processes are in yellow while those involving the recruitment of neuronal signaling partners and modulation of synaptic adaptation are in green. Immune and inflammatory-linked events are in blue. Lastly, changes at the level of cerebral cortex are shown in red.

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