Schizophrenia neurotransmitters

For many years it was believed that the brain mechanisms underlying the effects of psychedelic hallucinogens and dissociative anesthetics were separate and distinct. Indeed, there has been considerable debate about which represents the best drag model of schizophrenia. However, recent data show that the two classes of psychotomimetic drags share a common final pathway involving an increase in the release of the excitatory neurotransmitter glutamate. 

How the different neurotransmitters may be involved in the initiation and maintenance of some brain disorders, such as Parkinson s disease, epilepsy, schizophrenia, depression, anxiety and dementia, as well as in the sensation of pain, is then evaluated and an attempt made to see how the drugs which are used in these conditions produce their effect by modifying appropriate neurotransmitter function (section C). The final section (D) deals with how neurotransmitters are involved in sleep and consciousness and in the social problems of drug use and abuse. 

In the vertebrate CNS monoamines have been associated with a number of physiological functions (reviewed in Kandel et al., 1991). Serotonin has functions associated with mood, pain, sleep, learning, and memory. Dopamine has functions associated with schizophrenia, Parkinson s disease, and cocaine addiction. In vertebrates, dopamine is further metabolized into two additional neurotransmitters, norepinephrine and epinephrine. Norepinephrine increases the excitability of cells in response to sudden sensory input such as fear. Epinephrine has been identified in specific neurons of the brain, but the function of these cells is unknown. In addition, AADC has also been found in a class of neurons that do not have any of the four neurotransmitters discussed above (Jaeger et al., 1983). These neurons may use one of the trace amines, tyramine, tryptamine, or phenylethylamine, as a neurotransmitter. 

Some intracellular signal transduction molecules are reduced in schizophrenia. The release of neurotransmitters is regulated by a family of proteins that coordinate vesicular trafficking (see Ch. 9). Of these, the expression of complexin I and II appears to be decreased in prefrontal cortex and subfields of the hippocampal formation, and the ratio of complexin I to complexin II is elevated in the hippocampus [35], SNAP-25 (Synaptosomal Associated Protein, kDa 25) has inconsistently been found to be down-regulated in both these regions. Synapsin expression is also reduced, but more robust decrements have been observed in bipolar disorder (Ch. 55). 

Substance P, an undecapeptide, is abundant both in the periphery and in the central nervous system. It is usually co-localized with one of the classical neurotransmitters, most commonly serotonin. Substance P is thought to have a role in the regulation of pain, asthma, psoriasis, inflammatory bowel disease and, in the CNS, emesis, migraine, schizophrenia, depression and anxiety. The substance-P-preferring receptor neurokinin-1 has been focused on most intensively in drug development, and existing... 

Sigma Nonselective sigma Rat brain Inflammation, depression, schizophrenia, amnesia, stroke, cancer, ulcer, pain, diabetes Regulation of motor function, smooth muscle contraction, neurotransmitter release, neuroprotection... 

Traditionally, most affective disorders have been treated with compounds that resemble the neurotransmitters that are deficient or in excess in specific brain regions. The aberrant levels of neurotransmitters (or their receptors), such as norepinephrine, dopamine, acetylcholine, and serotonin, have correlated with behavioral symptoms of schizophrenia, depression, anxiety, sleep disorders, motor dysfunctions, attention difficulties, and cognitive disorders. Most drugs discovered for these disorders resulted from screening compounds directly in rodent behavioral models that mimic the behavior of the disease. In these cases, the molecular target" or mechanism of action was assumed to be the deficiency or excess of a neurotransmitter. 

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). 

Probably the greatest advances in psychiatric medications of the last 15 years have involved the neurotransmitter serotonin. First was the arrival of serotonin-specific antidepressants with fewer side effects and greater safety than their predecessors. More recently, atypical antipsychotics have highlighted the importance of serotonin-dopamine interactions in the optimal treatment of schizophrenia and other psychotic disorders. While these are indeed significant advances, medications that alter serotonin activity are not without their own side effect burden. 

Lastly, studies on the different polymorphic forms of the synapsins, that organize the mobilization of neurotransmitter vesicles thereby regulating neurotransmitter release, could account for some of the subtle changes in neurotransmission that occur in schizophrenia. However, to date linkage analysis studies have failed to reveal any positive associations between the various polymorphisms of the synapsin gene and schizophrenia. 

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