Dopamine (DA) is a small-molecule neurotransmitter involved in the control of both motor and emotional behavior. Despite the large number of crucial functions it performs, this chemical messenger is found in a relatively small number of brain cells. In fact, while there are a total of 10 billion total cells in the cerebral cortex alone, there are only one million dopaminergic cells in the entire brain.
Though small in number, dopaminergic cells are well dispersed among four major tracts in the brain. The nigrostriatal tract begins in the substantia nigra. These neurons extend to the putamen and caudate nucleus and are involved in the fine tuning of movement. The breakdown of neurons in this pathway is associated with the tremors, rigidity, bent posture, and slowness of movement characteristic of Parkinson's Disease.
The neurons in the tuberoinfundibular tract have cell bodies in the arcurate nucleus of the hypothalamus and extend to the pituitary stalk. These cells are involved in the control of hormones.
There are two dopaminergic tracts within the mesolimbocortical system. Both are involved in motivated and emotional behavior, and in organized thought processes. The mesolimbic tract begins in the ventral tegmental area and projects to many components of the limbic system. The mesocortical system also stems from the ventral tegmental area, but then projects to the neocortex, mostly to the prefrontal areas of the neocortex. Excess dopaminergic transmission within the two tracts of the mesolimbocortical system is associated with the disordered thought and inappropriate emotional behavior characteristic of schizophrenia.
Like all small-molecule neurotransmitters, dopamine (DA) is synthesized in the nerve terminal and stored there until an action potential arrives. Once released into the synaptic cleft, receptors on the postsynaptic cell recognize and interact with the DA molecules to cause depolarization of the postsynaptic cell and the initiation of a new action potential.
Six dopaminergic receptors have been well-characterized. All of these receptors, known as D1, D2a, D2b, D3, D4, and D5, are metabotropic, or G-linked, named so because they are linked to heterotrimeric GTP-binding (G) proteins. G-proteins relay signals received by receptors at the cell surface to effector molecules within the cell, often setting off a cascade of intracellular reactions. In this section, we will use the D1 receptor to illustrate one way that metabotropic receptors, and the proteins they are linked to, can indirectly open the ion channels necessary to cause a wave of depolarization.