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Increasing evidence suggests the involvement of the basal ganglia in HIV-1-infected patients. We used SIV-macaques, an animal model of HIV-1 infection, to investigate changes in CSF biogenic amine metabolites over time and compared them with control animals. The dopamine and serotonin metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), were analysed by reverse-phase chromatography with electrochemical detection. DOPAC concentrations were significantly increased in SIV-infected animals compared with controls. 5-HIAA and HVA remained unchanged. However, the longitudinal assessment of metabolites up to 3 months post-infection revealed a significant increase in 5-HIAA. Our results reflect the effects of SIV early stage infection on monoamine systems in brain and further validate the simian model for AIDS research.

Two cases of severe dystonia and dyskinesia were treated with talipexole, a dopamine autoreceptor agonist, and the metabolites of dopamine, norepinephrine, and serotonin in cerebrospinal fluid (CSF) were determined. Despite significant reductions in these metabolites in CSF, behavioral amelioration of these cases could not be observed. The present findings argue for further studies to explore the clinical usefulness of dopaminergic agonists such as talipexole.

Metabolites of selected neurotransmitters (5-HIAA, HVA and DOPAC) and beta-endorphin were measured in the CSF of 39 chronic pain patients and compared to controls. Twelve of the pain patients also fulfilled criteria for major depression. The concentration of 5-HIAA was increased in female but not male pain patients; there was no significant difference in the CSF concentrations of HVA and DOPAC. The presence of depression did not influence the concentrations of neurotransmitters. No correlation was found between the concentrations of monoamine metabolites and beta-endorphin. However, there was a positive correlation between 5-HIAA and HVA in controls and chronic pain patients without depression but not in depressed patients. It is concluded: chronic pain states are associated with elevation of CSF 5-HIAA in female patients; depression abolishes a positive correlation between 5-HIAA and HVA.

Brain serotoninergic neurons are known to participate in cardiovascular regulation. Administration of the serotonin precursor 5-l-hydroxytryptophan in conjunction with the monamine oxidase inhibitor phenelzine and the selective peripheral l-amino acid decarboxylase inhibitor carbidopa has been shown to raise the repetitive extrasystole threshold in the canine heart. The present investigation demonstrates that this drug regimen increases the cerebrospinal fluid concentration of serotonin and its major metabolite, 5-hydroxyindoleacetic acid, by 330 and 830%, respectively. By contrast, cerebrospinal fluid concentrations of norepinephrine and its major brain metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate, and of dopamine's metabolite, 3, 4-dihydroxyphenylacetic acid, were not significantly altered. Concomitantly, the ventricular fibrillation threshold was elevated by 42% and the effective refractory period prolonged by 7%. Efferent sympathetic neural activity was suppressed in the normal heart (from 7.9 +/- 1.3 to 3.9 +/- 1.1 impulses/s). The surge in sympathetic activity associated with acute myocardial ischemia was markedly attenuated. These results indicate that enhancement of central serotoninergic neurotransmission can reduce the susceptibility to ventricular fibrillation mediated through a decline in sympathetic neural traffic to the heart.