Regulation of Motor Behavior by Dopamine Receptor Subtypes

The neurotransmitter dopamine mediates various behavioral functions in the central nervous system (CNS). The major dopamine pathway involved in motor function is the nigrostriatal pathway, which originates from the substantia nigra and is the primary source of dopaminergic innervation of the dorsal striatal neurons (1–4). It plays an important role in regulating motor behavior and its deterioration is the major cause for the motor symptoms of Parkinson’s disease (5, 6). The mesolimbic pathway, which originates from neurons of the ventral tegmental area (VTA), innervates the ventral striatum, nucleus accumbens, olfactory tubercle, and parts of the limbic system, and is most probably involved in emotional and motivational aspects of behavior (7, 8). It may well contribute to the etiology of schizophrenia and serve as the substrate for neuroleptic drug actions (9, 10) along with the mesocortical pathway, which also originates in VTA and projects most densely to the prefrontal cortex (11). This terminal area may be involved in certain aspects of learning and memory (12, 13). Dopamine agonists have been used to ameliorate the major symptoms of Parkinson’s disease, whereas dopamine antagonists, the standard therapy for schizophrenia, often produce motor side effects; reminiscent of Parkinson’s disease. Through its action in these different neural pathways in the CNS, dopamine activates a broad range of motor behaviors.