Of all the rich chemicals in the amazing organ we call the brain, dopamine plays one of the most dramatic roles. Too little dopamine can cause slowed movement, apathy and lack of motivation. Too much dopamine is associated with schizophrenia and other mental illnesses. The correct balance of dopamine gives our brain and nervous system plasticity, the ability to move and think effortlessly and to keep a healthy balance in our emotions. The exotic brain chemistry that produces this range of behaviors is complex but well-understood enough so that new therapies for dopamine imbalances may soon be developed. This will be good news for depressives, Parkinson's disease patients and addicts seeking wellness.
Dopamine's Effects on Nervous System
Dopamine is a key neurotransmitter in the brain that affects physical movement, emotional response and the ability to experience pleasure or pain. Levels of dopamine are regulated by the interaction of the adenosine and dopamine system. Too little dopamine is a sign of Parkinson's disease; too much dopamine is characteristic of schizophrenia and some other mental disorders.
"Recreational" drugs like cocaine, amphetamines, heroin and alcohol all affect the dopamine system and cause different effects from euphoria to agitation, depending on how well the drugs mimic dopamine and the specific dopamine receptors that are either stimulated or blocked, according to the University of Texas Addiction Science Research and Education Center.
Dopamine agonists are drugs that act directly to stimulate dopamine receptors. L-DOPA is a drug that is given to Parkinson's disease patients to replace the missing dopamine in their brains.
Antagonists Reverse Dopamine Effects
Dopamine antagonists are drugs that reverse the effects of dopamine in the brains of patients such as schizophrenics whose systems overflow with the neurotransmitter. These drugs attach to dopamine receptors to block the effects of too much dopamine in the system. These drugs blunt the overproduction of dopamine to create a balance within the adenosine and dopamine system.
A naturally-occurring enzyme called monoamine oxidase, or MAO, quickly breaks down dopamine, but a drug called deprenyl reverses the effects of MAO, increases the level of dopamine and is effective in slowing the progression of Parkinson's disease, according to the University of Texas. Higher doses of deprenyl augment the beneficial effects of dopamine in Parkinson's patients.
Sensitization and Tolerance
Street drugs such as cocaine and amphetamine also boost production of dopamine by preventing its reuptake, or recycling, into neurons in the brain. Dopamine levels remain high for long periods of time and generate pleasurable feelings. Methylphenidate, often prescribed to treat children with attention deficit disorder/hyperkenisis disorder, or ADD/HD, also stimulates production of dopamine.
The way that neurons respond to dopamine is at the heart of drug addiction. Long-term treatment with dopamine antagonists causes the brain to produce more dopamine receptors, which are more sensitive to dopamine. This process is called sensitization.
Tolerance, or desensitization, results when the effects of repeated use of a drug decline sharply as the nervous system struggles to maintain equilibrium. Both sensitization and tolerance can develop after just one exposure to a drug.
The Adenosine-Dopamine System
Imbalances in the adenosine-dopamine system can have profound effects on motivation and apathy. The spaced-out condition of a drug addict and the slowing of psychomotor reflexes in Parkinson's disease patients seem to share a similar chemistry.
A 2006 study at the University of Connecticut using rats to test the effects on effort-related eating behavior found that rats whose dopamine had been depleted chose not to perform tasks with a high food reward if they required a high response. The animals were injected with the antipsychotic drug haloperidol, which is a dopamine antagonist, or inhibitor.
But administration of an adenosine antagonist drug reversed the effects of haloperidol in a dose-related pattern. In other words, the test demonstrated how bringing the adenosine-dopamine system into balance reversed the apathy and low energy of the rats.
Implications for New Drugs
The scientists believe this finding "may have implications for the treatment of psychiatric symptoms such as psychomotor slowing," they said in their paper published in the Oct. 27, 2006, issue of Psychopharmacology. They speculate that adenosine antagonist drugs might be effective against symptoms of depression and other psychiatric illnesses.
"There are striking similarities between the characteristics of parkinsonian bradykinesia (slowness) and psychomotor slowing in affective disorders," the authors noted.
