Dopamine, like serotonin, is an monoamine neurotransmitter. Dopamine, however, is a cateholamine. Scientific interest in dopamine is usually centered around the fact that it is involved in the brain's reward circuit. For this reason, dopamine is strongly implicated in connection with highly addictive substances. Research indicates that dopamine is the primary neurotransmitter affected by stimulants like amphetamines and cocaine. Because of this amphetamine connection and because of MDMA's amphetamine properties, dopamine is a good candidate for MDMA's neurological effects.
Dopamine synthesis begins when the
amino acid tyrosine enters dopaminergic neurons. Inside the neuron, the
enzyme tyrosine hydroxylase adds a
hydroxyl group to tyrosine and it becomes 3,4-dihydroxyphenylalanine (DOPA). The final step in the creation of dopamine involves an enzyme called aromatic L-amino acid decarboxylase, which removes a
carboxyl group from DOPA. The final product, dopamine, is now transported down the
axon to where it wait for an
action potential to signal its release. After dopamine has been released and had its effect on neighboring neurons, it is pumped back into the dopaminergic axons by an active
reuptake mechanism. Because the reuptake of dopamine does not involve deactivation of the dopamine molecule, dopamine can affect the cells that it enters in this reuptake process. As you will see in the section on neurotoxicity, this characteristic of dopamine could be an important factor in the potential toxicity of MDMA.
There are two main systems in the brain that involve dopaminergic neurons. These two systems are the nigrostriatal sytem and the mesolimbic system. Neurons of the nigrostriatal system originate in the substantia nigra and terminate in the caudate nucleus and the putamen, both of which are located in the forebrain.
The mesolimbic system extends from the ventral tegmental area and has terminal buttons that reach to many different areas of the brain. The areas that recieve input from the dopaminergic neurons of the VTA include the nucleus accumbens, the amygdala and the hippocampus.
The main effects of the dopaminergic systems involve movement and the internal reward system. The first set of dopaminergic neurons mentioned above, the nigrostriatal system, affects areas of the brain that are responsible for the control of voluntary movement. When these neurons are damaged, the result can be a loss of movement control like that seen in sufferers of
Parkinson's disease. The mesolimbic system is the one that includes the reward system. This system consists of neurons that terminate in the nucleus accumbens. This system also includes connections with the amygdla, which is involved in emotional responding, and the hippocampus, which is involved in memory processing. The combination of these elements: emotional responding, memory and the internal reward system, results in a circuit that increases the probability that whatever behavior triggers activity in it will be repeated. When presented with this model of dopaminergic function it is not difficult to believe that drugs that trigger dopamine release will produce pleasurable responses and be likely to be used again.
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