Human Brain & Mind
  • Neurotransmitters Dopamine

    Dopamine circuits are more specific and better organized than NE and serotonin systems. Dopamine neurons are involved in controlling movement, regulating memory, sexual and reward-seeking behaviors and the regulation of pituitary hormones. Increased dopamine activity is associated with schizophrenia.

    Decreased dopamine activity in a specific movement controlling circuit originating from cells in the substantia nigra are associated with Parkinson's disease. Slowing of thinking and movement and depression often precede the more obvious movement disorder which characterizes the disease. The main treatment has been to replace the missing dopamine with l-Dopa (levodopa). With time and disease progression, however, dopamine replacement becomes less efficacious and new adverse effects, including the development of motor fluctuations and drug-induced involuntary movements (dyskinesias) emerge.

    When dopamine is slightly modified to 6-hydoxy dopamine, it becomes a potent neurotoxin that can kill dopamine producing neurons. The toxicity of 6-hydroxydopamine involves the generation of reactive oxygen radicals, the impairment of mitochondrial function, and enzyme inhibition. Antioxidants, including catalase, vitamin E, and ascorbic acid, provided protection against 6-OHDA-induced toxicity.

    Liao et al suggested that: Formation of 6-hydroxydopamine (6-OHDA) in the striatum following methamphetamine treatment plays a role in methamphetamine-induced nigrostriatal dopaminergic toxicity. Inhibiting both monoamine oxidase with pargyline and catechol-O-methyl-transferase with pyrogallol lead to an accumulation of 6-OHDA in the striatum; this effect was increased by the addition of methamphetamine which is a potent dopamine releaser.

    Dopamine Increased

    Increased dopamine activity in the brain stem will cause unpleasant symptoms suggesting digestive tract problems - nausea, vomiting, hiccups, excessive salivation and a burning tongue. Increased dopamine in the motor circuits will tend to produce odd, involuntary movements, muscle twitching and bizarre posturing. Early signs of increased dopamine activity include agitation with critical, suspicious thinking and depression. Increased sexual drive and antisocial aggression may occur with disordered arousal.

    Dopamine and Schizophrenia

    All discussions of schizophrenia should begin with the recognition is that the diagnosis is often uncertain and covers a range of disorders that have different causes and different consequences. The focus has been on dopamine neurons and drugs that block dopamine. Few people with the diagnosis escape drug treatment and psychiatrists generally believe that schizophrenics have to take drugs every day for the rest of their lives. This is an irrational belief that obstructs the study of the natural course of the disorder and prevents the discovery of better methods of management. You can argue two ways:

    1. Drugs used to treat schizophrenics are wonderful inventions that control the disease and allow patients to live in the community.

    2. Antipsychotic drugs are chemical straight-jackets that are toxic and leave patients more disabled than they would have been if no drugs were ever used.

    A corollary to argument 2 is that if other solutions were developed for schizophrenics, such as diet revision, nutrient supplementation, and rehabilitation in natural settings, better long-term results may be achieved.

    Phenothiazines were the first drug class available to treat schizophrenia. They were called antipsychotics, major tranquilizers, and neuroleptics. Chlorpromazine was the grand-daddy drug and numerous offspring were developed and marketed. These drugs have multiple modes of action and the antipsychotic effect is attributed to dopamine blocking. With long term use, drug-induced Parkinson's disease is a major, disabling adverse effect.

    Kapur suggests that delusions develop when excessive dopamine release occurs in response to mundane events. Delusions are the stories that patients construct to explain increased salience of common events. Antipsychotic drugs block dopamine-2 neuroreceptors and reduce the salience of ordinary experiences: the patient may say that the government continues to spy on him, but that it doesn't bother him anymore. Kapur claims that resolution of symptoms occurs within the first week of antipsychotic treatment.

    All early antipsychotics inhibit dopamine (DA) neurotransmission by blocking postsynaptic DA receptors. Other neurotransmitter systems, such as those for serotonin (5-HT), glutamate, noradrenaline and acetylcholine, are also implicated, and atypical antipsychotics are also antagonists of serotonin (5-HT) receptors. Blocking DA receptors in some brain regions is also responsible for negative effects such as Parkinson's effects and hormonal changes.

    Excessive Use of Dopamine Blocking Drugs

    Newer dopamine-blocking antipsychotic drugs are prescribed inappropriately and excessively to children and elderly patients. The “atypical antipsychotics,” clozapine, olanzapine, quetiapine and risperidone have all been used to treat elderly patients, especially those with dementia. There is no evidence that any of these drugs will alleviate dementia in any way. They are used, for example, as “chemical straight jackets” to immobilize nursing home residents. Among the problems created by these drugs are Parkinson’s disease, weight gain, hyperglycemia and diabetes 2. Janssen-Ortho, the company that markets Risperdal (risperidone), issued drug safety information bulletin [i] linking the drug to increased risk of strokes in elderly patients. Since there is significant doubt that this drug should be used in any elderly patients, the increased risk of diabetes and stroke is a definitive contraindication. The strength of the association between antipsychotics and diabetes varies. A number of reports implicate chlorpromazine, clozapine, and olanzapine. An Ontario study involving 20,000 patients in nursing homes revealed that 25% of the residents are prescribed antipsychotic medications within the first year of admission. [ii]

    [i] Janssen-Orthos. Risperdal and Cerebrovascular adverse events in Placebo-controlled dementia trials. Letter Oct. 11, 2002
    [ii] Murray, T. Antipsychotic use high in Ont. Nursing homes. Medical Post May 25, 2004. Reporting on a study by researchers at the Institute for Clinical Evaluative Sciences in Toronto, Ontario, conducted between 1998 and 2000.

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