Role of tryptaminergic mechanisms in the elements of the behavioural syndrome evoked by tryptophan and a monoamine oxidase inhibitor [proceedings].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to T J Crow.
Explore the source record for details and available documents.
On the basis of post-mortem studies it has been proposed that the central deficit in schizophrenia may be in noradrenergic transmission. It has also been proposed that there is a substantial central contribution to the excretion of the noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and more particularly of its sulphate conjugate in man. There is throught to be a lesser central contribution to the excretion of the other major noradrenaline metabolites, vanillylmandelic acid (VMA) and the glucuronide conjugate of MHPG. A strong negative correlation was found between severity of illness in a group of 18 unmedicated chronic schizophrenic patients and their 24-h excretion of MHPG-sulphate but not of MHPG-glucuronide or VMA. However there was no significant difference in the mean excretion of MHPG conjugates or of VMA between the schizophrenic group and an institutional control group. This supports the idea of a relation between MHPG-sulphate excretion and central noradrenergic activity, but suggests that reduced brain noradrenaline turnover is neither necessary nor sufficient for schizophrenia to occur. One possible explanation is that reduced turnover pre-disposes towards a more severe illness in schizophrenics.
Explore the source record for details and available documents.
By comparison with age-matched controls in employment, 17 institutionalised schizophrenic patients were shown by computerised axial tomography of the brain to have increased cerebral ventricular size. Within the group of schizophrenic patients increased ventricular size was highly significantly related to indices of cognitive impairment.
The antipsychotic actions and extra-pyramidal side-effects of neuroleptic drugs are strongly correlated with their ability to block central dopaminergic transmission. It is argued that the former are more closely related to actions on dopaminergic mechanisms in the "mesolimbic dopamine" system, and the latter to similar actions in the striatum. Although the amphetamine psychosis closely resembles paranoid schizophrenia and may be due to excess dopamine release, clinical, biochemical, and endocrine studies suggest that dopaminergic overactivity is not a necessary concomitant of schizophrenic illnesses. It is suggested that the primary defect in schizophrenia does not lie in the dopamine neuron. It remains to be excluded that the receptors, particularly in the mesolimbic dopamine areas, become supersensitive, or that there is a deficit in a system which normally acts in antiagonism to the to the mesolimbic dopamine system.
Platelet monoamine oxidase (MAO) activity was investigated in a series of 60 patients with chronic schizophrenic illnesses free from neuroleptic medication, and 70 normal controls. No significant differences in platelet MAO activity or in substrate preference were detected between patients and controls, using tryptamine and tyramine as substrates. Platelet MAO activity did not distinguish patients with positive symptoms from those with negative symptoms alone and did not show any relationship with severity of disease or with a number of clinical features. These findings suggest that low platelet MAO activity cannot be regarded as a genetic marker for schizophrenia. Important determinants of platelet MAO activity yet to be discovered may have contributed to the discrepancies in recent observations of platelet MAO activity in schizophrenia.
The hypothesis has recently been advanced that increased activity of central dopaminergic mechanisms underlies the symptomatology of the schizophrenias. The evidence that dopaminergic transmission in the corpus striatum is impaired in Parkinson's disease suggests that observations on the relationship between Parkinson's disease and schizophrenia may illuminate the patholophysiology of the latter disease. Four cases are reported in which an illness with schizophrenic features developed in the setting of longstanding Parkinson's disease; attention is drawn to earlier reports of schizophrenic illnesses occurring as postencephalitic sequelae in the presence of a parkinsonian syndrome. These observations appear to conflict with the view that increased dopamine release in the striatum is necessary for the expression of schizophrenic psychopathology, but do not exclude the possibility that increased transmission may occur at other dopaminergic sites in the brain, for example the nucleus accumbens, tuberculum olfactorium or cerebral cortex. Similarly the dopamine receptor blockade hypothesis of the therapeutic effects of neuroleptic drugs cannot be maintained with respect to an action in the striatum in view of the differences between the actions of thioridazine and chlorpromazine in this structure, but may be tenable for actions at extra-straital sites.
1. Unit activity and excitability were studied at the midlateral and suprasylvian cortex of naive, blink-conditioned and "randomization" cats. The latter received the same CS and US as did the conditioned animals, but in random temporal order and with random intertrial intervals with mean comparable to that used for conditioning. The randomization group failed to develop a blink CR. 2. With conditioning, spontaneous and evoked unit discharges were increased above levels found in naive animals. Correspondingly, levels of extracellularly injected current required to elicit a spike discharge were lower in conditioned than in naive animals. In addition, in the conditioned animals, the degree of enhancement of evoked activity and excitability was found to be greatest in the units that responded to the CS, as opposed to units that responded to another auditory stimulus of equal intensity but of no special behavioral significance vis-a-vis the conditioned reflex. 3...
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.