Synaptosomal uptake of norepinephrine and 5-hydroxytryptamine and synthesis of catecholamines during benzodiazepine treatment

1978 ◽  
Vol 56 (5) ◽  
pp. 777-784 ◽  
Author(s):  
R. B. Rastogi ◽  
Y. D. Lapierre ◽  
R. L. Singhal
Keyword(s):  
Locomotor Activity ◽  
Homovanillic Acid ◽  
Single Injection ◽  
Brain Areas ◽  
Catecholamine Synthesis ◽  
Endogenous Level ◽  
Hydroxyindoleacetic Acid ◽  
Previously Treated ◽  
Low Levels ◽  
Chronic Diazepam

Administration of diazepam (10 mg/kg, sc) acutely or for 22 consecutive days decreased spontaneous locomotor activity and presumably the release of norepinephrine and dopamine as evidenced by increased levels of these amines in crude synaptosomes and low levels of their metabolites, 4-hydroxy-3-methoxyphenylglycol in brain and homovanillic acid in striatum of rats. Acute or chronic diazepam elevated the levels of synaptosomal 5-hydroxytryptamine by 21 and 50%, respectively, suggesting that the release of this indoleamine was also diminished. Whereas a single injection of diazepam failed to alter the synaptosomal uptake of 5-[3H]hydroxytryptamine or rate of synthesis of this indoleamine, repeated exposure for 22 days enhanced it by 31 and 28%, respectively. Acute diazepam treatment also enhanced 5-hydroxyindoleacetic acid levels in hypothalamus, pons–medulla, and midbrain of rats. The endogenous level of tryptophan in P2 pellet also was increased (by 117%) in chronic diazepam-treated rats. Diazepam given acutely or chronically failed to change the rate of catecholamine synthesis. However, discontinuation of diazepam for 48 h in rats previously treated for 20 days significantly increased locomotor activity and synaptosomal catecholamine synthesis above the values of 'treated' as well as normal control animals. Despite their increased synthesis, the synaptosomal levels of norepinephrine and dopamine in 'withdrawn' groups were decreased to 46 and 62%, respectively. This could presumably be due to a compensatory release of these monoamines and partly to altered uptake of norepinephrine which was diminished by 24%. Additionally, the levels of homovanillic acid in striatum and 4-hydroxy-3-methoxyphenylglycol in brain were enhanced to 196 and 193%, respectively, taking the values of chronically exposed rats as 100%. Withdrawal of rats from diazepam decreased the rate of synthesis of 5-hydroxytryptamine and the level of 5-hydroxytryptamine within the crude synaptosomes; the latter could be attributed to enhanced release and impeded uptake of this indoleamine. The view gains support from enhanced levels of the metabolite 5-hydroxyindoleacetic acid seen in several brain areas of withdrawn rats.Our data suggest that diazepam exerts its central effects on mood and behaviour by impairing the release of catecholamines and 5-hydroxytryptamine. It is also suggested that enhanced release and decreased uptake of these monoamines may, in part, be responsible for the hyperexcitability seen during the 'rebound' phase in anxious patients withdrawn from benzodiazepine therapy.

Alterations in brain dopamine and serotonin metabolism during the development of tolerance to human β-endorphin in rats

1978 ◽  
Vol 56 (6) ◽  
pp. 1067-1071 ◽  
Author(s):  
Glen R. Van Loon ◽  
Errol B. De Souza ◽  
Chul Kim
Keyword(s):  
Homovanillic Acid ◽  
Single Injection ◽  
Serotonin Release ◽  
Serotonin Metabolism ◽  
Brain Dopamine ◽  
Brain Areas ◽  
Dopamine Metabolites ◽  
Initial Injection ◽  
Hydroxyindoleacetic Acid ◽  
Development Of Tolerance

Repeated intracisternal injections of human β-endorphin lead to development of tolerance with respect to the catalepsy, analgesia, and hypothermia which are seen following a single injection. The initial injection of β-endorphin results in increases in the dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in neostriatum, as well as increases in the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in hypothalamus and brainstem and a decrease in 5-HIAA in hippocampus. In the present study, we report changes in metabolism of dopamine and serotonin in specific brain areas during the development of tolerance to β-endorphin. Thus, the development of tolerance to β-endorphin with respect to catalepsy, analgesia, and hypothermia may be mediated by development of tolerance to the effects of β-endorphin on brain dopamine and serotonin release.

Homovanillic acid and 5-hydroxyindoleacetic acid in the ventricular CSF of comatose patients with obstructive hydrocephalus

1980 ◽  
Vol 52 (5) ◽  
pp. 635-641 ◽  
Author(s):  
Tetsuji Inagawa ◽  
Susumu Ishikawa ◽  
Tohru Uozumi
Keyword(s):  
Head Injury ◽  
Homovanillic Acid ◽  
Obstructive Hydrocephalus ◽  
Third Ventricle ◽  
Cerebrovascular Lesions ◽  
Content Type ◽  
Hydroxyindoleacetic Acid ◽  
Csf Levels ◽  
Low Levels ◽  
The Relationship

✓ Ventricular cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined every 2 to 4 hours over a period of 1 to 4 days in 12 patients, consisting of seven cases of brain tumor, two cases of cerebrovascular disease, and three cases of head injury. The concentrations of HVA and 5-HIAA varied with time in all cases, and significant correlations were found between the two values in eight cases. However, the relationship between variations of HVA and 5-HIAA levels and rhythms of sleep and waking could not be clarified. Both HVA and 5-HIAA concentrations varied at high levels in two patients whose CSF flow was completely blocked by tumor at the site of the fourth ventricle and aqueduct, respectively. On the contrary, in a case with craniopharyngioma in the third ventricle which blocked the bilateral foramina of Monro, although the HVA values were high, the 5-HIAA values varied at low levels. Of five comatose patients, two had cerebrovascular lesions and three had sustained head injury, and, in four of the five, the values of either one or both of HVA and 5-HIAA were low, but in the fifth case the 5-HIAA value was high. Estimation of HVA and 5-HIAA concentrations in ventricular CSF may be a valuable tool in the investigation of brain monoamine metabolism. However, many factors must be considered in the interpretation of results of clinical studies.

Serotonin and 5-hydroxyindoleacetic acid concentrations in individual hypothalamic nuclei and other brain areas of rat

1984 ◽  
Vol 40 (11) ◽  
pp. 1288-1290 ◽  
Author(s):  
K. Oomagari ◽  
H. Uchimura ◽  
T. Matsumoto ◽  
H. Yokoo ◽  
M. Hirano ◽  
...  
Keyword(s):  
Brain Areas ◽  
Hypothalamic Nuclei ◽  
Hydroxyindoleacetic Acid

Noradrenergic Overactivity in Chronic Schizophrenia: Evidence Based on Cerebrospinal Fluid Noradrenaline and Cyclic Nucleotide Concentrations

1980 ◽  
Vol 137 (4) ◽  
pp. 346-351 ◽  
Author(s):  
U. C. R. Gomes ◽  
B. C. Shanley ◽  
L. Potgieter ◽  
J. T. Roux
Keyword(s):  
Cerebrospinal Fluid ◽  
Cyclic Nucleotides ◽  
Homovanillic Acid ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Chronic Schizophrenia ◽  
Evidence Based ◽  
Chronic Schizophrenics ◽  
Hydroxyindoleacetic Acid ◽  
Lumbar Cerebrospinal Fluid

SummaryConcentrations of noradrenaline (NA), homovanillic acid, 5-hydroxyindoleacetic acid and cyclic nucleotides were determined in lumbar cerebrospinal fluid (CSF) from acute and chronic schizophrenics and various groups of psychiatric and non-psychiatric control subjects. Statistically significant increases in NA and cyclic adenosine monophosphate were found in CSF from chronic schizophrenics compared to all other groups. These results were shown by statistical analyses to be unrelated to medication. They may be interpreted as evidence for noradrenergic overactivity as a possible primary abnormality in chronic schizophrenia.

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