Cerebrospinal fluid dopamine levels

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. 

Neurotransmitter Transporters. Figure 3 Dopamine turnover at a presynaptic nerve terminal, (a) Dopamine is produced by tyrosine hydroxylase (TH). When secretory vesicles are filled, they join the releasable pool of vesicles at the presynaptic membrane. Upon exocytosis, the diffusion of released dopamine is limited by reuptake via DAT. (b) If DAT is inactive, dopamine spreads in the cerebrospinal fluid but cannot accumulate in secretory vesicles. This results in a compensatory increase of dopamine hydroxylase activity and a higher extracellular dopamine level mice with inactive DAT are hyperactive. 

Once returned to the presynaptic terminal, dopamine is repackaged into synaptic vesicles via the vesicular monoamine transporter (VMAT) or metabolized to dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO). Two alternative pathways are available for dopamine catabolism in the synapse, depending on whether the first step is catalyzed by MAO or catechol-O-methyltransferase (COMT). Thus, dopamine can be either deaminated to 3,4-dihydroxyphenylacetic acid (DOPAC) or methylated to 3-methoxytyramine (3-MT). In turn, deamination of 3-MT and methylation of DOPAC leads to homovanillic acid (HVA). In humans, cerebrospinal fluid levels of HVA have been used as a proxy for levels of dopaminergic activity within the brain (Stanley et al. 1985). 

Argentiero V, Tavolato B Dopamine (DA) and serotonin metabolite levels in the cerebrospinal fluid (CSF) in Alzheimer s presenile dementia under basic conditions and after stimulation with cerebral cortex phospholipids. J Neurol 224 53-58, 1980... 

It has not been possible to show abnormalities in overall dopamine content of brains of people with schizophrenia. Total dopamine content can, incidentally, only be measured at post-mortem (Scott 2006), and overall such studies have not shown any differences between people with schizophrenia and those without (Reynolds Czudek 1988). As one of the main researchers in the field put it, the dopamine content is found to be normal in the schizophrenic brain (Seeman 1995). Research into levels of dopamine metabolites in the cerebrospinal fluid,3 which initially claimed to find increased levels in people with schizophrenia, also proved to be inconclusive when people who had not been treated with drugs were investigated (Reynolds 1989 Tuckwell Koziol 1993). 

It is clear from these data that for AEA the relative regional abundance in the brain does not correlate with the distribution of CBIR. AEA levels in the brain are equivalent to those of other neurotransmitters such as dopamine and serotonin, but at least 10-fold lower than the levels reported for GABA and glutamate. AEA has also been found in peripheral tissues such as human and rat spleen, which expresses high levels of CB2R. Small amounts of AEA were also detected in human serum, plasma, and cerebrospinal fluid (Felder et al., 1996). 

---