Dopamine schizophrenia and

Like the monoamine hypothesis of depression, such a simple hypothesis was appeaUng but, perhaps predictably, a Uttle too simple to be true. Further research using a technique known as positron emission tomography (PET) showed the relationship between dopamine and schizophrenia is more complex. PET detects radioactive emissions of certain isotopes these isotopes are incorporated into a molecule and injected into a patient. The machine measures the radioactivity with detectors positioned aroimd the body. PET lets researchers study the distribution of certain molecules in Uving tissue since, imUke autoradiography, the tissue is not sliced and treated chemically. The amoimt of radioactivity must be small, however, to avoid harming the human subjects. 

Stimulant), act directly on dopamine transmission. Both cocaine and amphetamine block reuptake of dopamine, which means that more dopamine is available to activate postsynaptic receptors. Due to the links between excessive dopamine and schizophrenia, it comes as no surprise that the use of cocaine, amphetamine, and similar drugs such as crack (a form of cocaine) often lead to symptoms strongly resembling schizophrenia. 

The hypothetical link between dopamine and schizophrenia was forged by two reciprocally related findings. The first was that potent dopamine agonist stimulants like d-amphetamine and cocaine could cause a psychosis that was schizophrenia-like, in that it had auditory hallucinations and paranoia. The second was that the neuroleptic drugs that were effective in reversing both schizophrenia and stimulant-induced psychosis were dopamine blockers. Moreover, the antipsychotic potency of the neuroleptics was proportional to their binding affinity to the D2 receptor. 

Laruelle M, Kegeles LS, Abi-Dargham A. Glutamate, dopamine, and schizophrenia from pathophysiology to treatment. Ann N YAcad Sci. 2003 1003 138-158. 

Jaskiw, G. E., and D. R. Weinberger. 1992. Dopamine and schizophrenia—a cortically corrective perspective. Seminars in the Neurosciences 4 179-88. 

Knoble, MB and Weinberger, DR (1997) Dopamine, the prefrontal cortex and schizophrenia. J. 

Malhotra, A. K., Goldman, D., Buchanan, R.W. et al. (1998). The dopamine D-3 receptor (DRD3) Ser-9Gly polymorphism and schizophrenia a haplotype relative risk study and association with clozapine response. Mol. Psychiatry, 3, 72-5. 

Ishiguro H, Okuyama Y, Toru M, Ari-nami T. Mutation and association analysis of the 5 region of the dopamine D3 receptor gene in schizophrenia patients identification of the Ala38Thr polymorphism and suggested association between DRD3 haplotypes and schizophrenia. Mol Psychiatry 2000 5[4] 433—438. 

Determining the underlying rationale for studying a neuroreceptor system, e.g. the dopamine hypothesis for cocaine abuse and schizophrenia ... 

Dopamine is a major catecholamine neurotransmitter in the central nervous system (37) that is involved in the neuroregulation of locomotor activity, emotion, and neuroendocrine secretion (38,39). Clinically, dopaminergic drugs are used to treat Parkinson s disease and schizophrenia by activating or blocking dopamine receptors, respectively (40). 

TaIkowski, M. E., Mansour, H., Chowdari, K. V., et el(2006) Novel, replicated associations between dopamine Dj receptor gene polymorphisms and schizophrenia in two independent samples. Biol. Psychiatry. 60, 570-577. 

The two pioneer drugs for schizophrenia are chlorpromazine and reserpine. Reserpine is known to reduce the brain levels of norepinephrine, dopamine, and serotonin. Since reserpine is also effective in coping with some of the symptoms of schizophrenia, perhaps an abnormally high concentration of one or more of these monoamines is a contributing factor to this disorder. 

Solms (2000 see also Chapter 7) has observed that suppression of cortical dopaminergic afferents abolishes dreaming. Dopamine therefore appears to be a neurotransmitter keystone of the common features of REM sleep, dreaming and schizophrenia. 

CS291 Rodriguez De Fonseca, F., M. A. Gorriti, A. Bilbao et al. Role of the endogenous cannabinoid system as a modulator of dopamine transmission implications for Parkinson s disease and schizophrenia. Neurotox Res 2001 3(1) 23-35. 

Although the role of neurotransmitter dysfunction in schizophrenia remains an exciting and important avenue of exploration, we are only aware of one study of neurotransmitters in COS. Jacobsen and colleagues (1997a) measured cerebrospinal fluid (CSF) levels of HVA and 5-HIAA, metabolites of dopamine and serotonin, respectively. While the concentrations of these monoamine metabolites were similar to that seen in adults with schizophrenia, they did not change significantly with treatment. 

In 1976, Ian Creese, David R. Burt, and Solomon H. Snyder of Johns Hopkins University in Baltimore, Maryland, reported that the most effective schizophrenia medications are the ones that have the strongest affinity for dopamine receptors. Researchers also discovered drugs that increased the amount of dopamine inadvertently caused schizophrenic symptoms in patients. These findings led to the dopamine hypothesis of schizophrenia—too much dopamine causes schizophrenia. 

Technologies that examine a large number of metabolites at the same time are sometimes known as metabolomics. This term is similar to genomics, in which large numbers of genes are detected or studied simultaneously. Such studies are only in their beginning phases, and researchers do not yet understand if the differences they are finding in metabolites are critical or not. Dopamine and other brain chemicals are important in the development of schizophrenia, at least for some forms of the disease, but scientists do not yet know how. 

Neurochemists continue to improve the methods they use to measure and analyze chemicals of the brain. They have also developed techniques to study how neurons transmit messages across synapses to other neurons, and how these messages affect the recipients. Synaptic transmission is critical in brain function, and neurotransmitter imbalances have been associated with disorders such as depression and schizophrenia as well as drug abuse. Although the cause or causes of these conditions are not necessarily as simple as too much or too little of a certain neurotransmitter, chemicals such as dopamine and serotonin are undoubtedly involved. Neurotransmitters have been excellent starting points for further, ongoing studies into these issues. 

DasGupta K, Young A Clozapine-induced neuroleptic malignant syndrome. J Clin Psychiatry 52 105-107, 1991 Davis KL, Kahn RS, Ko G, et al Dopamine in schizophrenia a review and reconceptualization. Am J Psychiatry 148 1474-1486, 1991 Devinsky O, Honigfeld G, Patin J Clozapine-related seizures. Neurology 41 369-371, 1991... 

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