B. Anagnoste

Norepinephrine biosynthesis inhibition: effects on memory in mice.

Diethyldithiocarbamate, a dopamine beta hydroxylase inhibitor, decreases biosynthesis of norepinephrine in the brain. The effects of this inhibitor coincide with alterations in memory as demonstrated in single-trial passive avoidance in C57BL/6J mice.

Studies of amines in the striatum in monkeys with nigral lesions. The disposition, biosynthesis and metabolites of [3H]dopamine and [14C]serotonin in the striatum.

The effects of ventromedial tegmental lesions on the biosynthesis and disposition of biogenic amines in the striatum of monkeys were investigated. The concentrations of endogenous dopamine and of the intraventricularly injected [3H]dopamine were distinctly lower in the striatum on the lesion side than on the intact side.

The effect of trivastal, haloperidol and dibutyryl cyclic AMP on (14C)dopamine synthesis in rat striatum.

There is, of course, also the possibility that the dopamine receptors in the limbic system are blocked to a greater extent than those in the corpus striatum by clozapine but not by haloperidol. Finally, the results indicate that determinations of HVA in the corpus striatum and in the limbic system of rabbits may be of value in predicting the ability of neuroleptic drugs to induce in man extrapyramidal and antipsychotic actions, respectively. This work was supported by the Swedish Medical Research Council (B73-04X502-09B). Giinter Stock is a recipient of a traineeship from the European Training Program in Brain and Behaviour Research. For generous gifts of drugs we thank Dr. G. Stille, Dr. A. Wander, Ltd., Berne (clozapine) and Leo Ltd., Helsingborg (haloperidol). The excellent technical assistance of Mrs. Inger Oscarsson is gratefully acknowledged.

The effects of ventromedial tegmental lesions on the biosynthesis of catecholamines in the striatum

Abstract Following ventromedial tegmental lesions in the brain stem of monkeys, tyrosine hydroxylase activity is significantly lower on the lesion side of the caudate nucleus and putamen. The in vivo formation of dopamine-C 14 from tyrosine-C 14 is impaired on the lesion side in these two regions of the CNS. The present findings support the idea that ventromedial tegmental lesions produce a degeneration of dopamine neurons in the ipsilateral caudate nucleus and putamen.

CHARACTERISATION, LOCALISATION AND REGULATION OF CATECHOLAMINE SYNTHESIZING ENZYMES

Publisher Summary This chapter discusses a study analyzing characterization, localization and regulation of catecholamine synthesizing enzymes. In the study, aromatic L-amino acid decarboxylase (AADC) was purified from bovine adrenal glands. After immunization of rabbits with purified AADC (enzyme preparation obtained after polyacrylamide gel electrophoresis), specific antisera to AADC were obtained. Bovine AADC antiserum inhibits AADC activity from different tissues of various species. Immunochemical and immunohistochemical studies were applied to test whether the same enzyme catalyzes the decarboxylation of L-dopa and L-5-hydroxytryptophan (L-5HTP) or not. Earlier studies show that specific anti-serum directed against AADC inhibits L-Dopa and L-5HTP striatal decarboxylase activity proportionately. The immunohistochemical studies and the findings that 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine pathway causes a proportional reduction in striatal L-Dopa and L-5HTP decarboxylase activity, support the hypothesis that a single enzyme catalyzes the decarboxylation of both aromatic L-amino acids in the striatum. However, the current data does not exclude the possibility that in some regions of the brain an enzyme exists which catalyzes specifically either L-Dopa or L-5HTP decarboxylation.

Effect of harmaline in monkeys with central nervous system lesions.

Abstract Harmaline produced shivering in normal monkeys and intensified the resting tremor or evoked a resting tremor in monkeys with ventromedial tegmental lesions. In monkeys with such lesions, thalamic or globus pallidus destruction abolished the spontaneous tremor, blocked the harmaline-evoked tremor, but did not prevent the shivering induced by harmaline.

Studies on the regional biosynthesis and metabolism of catecholamines in the central nervous system of the monkey.

Nach intraventrikulärer Verabreichung von Tyrosin-C14 oder Dopamin-H3 wurden die Biosynthese und der Stoffwechsel des Katecholamins in verschiedenen Regionen des ZNS bei Affen (Cercopithecus sabaeus) untersucht. Die grössten Katecholaminmengen wurden aus Tyrosin-C14 im Nucleus caudatus gebildet. Ebenso ist dort, wie im Putamen, die Tyrosin-Hydroxylase-Aktivität am grössten. Die Bildung des Noradrenalins aus Dopamin konnte im Hypothalamus, Hirnstamm, sowie im Nucleus caudatus nachgewiesen werden. Die Verteilung des radioaktiven Dopamins entspricht nicht in allen Hirnregionen der Verteilung des endogenen Dopamins.

Tyramine-H3: Deaminated Metabolites in Neuroblastoma Tumors and in Continuous Cell Line of a Neuroblastoma

Neuroblastoma tumors, as well as cultured cells of neuroblastoma, contain high monoamine oxidase activity. The major deaminated metabolite of tyramine-H3 in the incubation mixtures with the tumors or with the cultured cells is p-hydroxyphenylacetaldehyde. Upon addition of reduced nicotinamide-adenine dinucleotide phosphate, the aldehyde was further metabolized by the reductive pathway to p-hydroxyphenylethanol, whereas upon addition of nicotinamide-adenine dinucleotide phosphate the aldehyde was only metabolized to a minor extent by the oxidative pathway to p-hydroxyphenylacetic acid. Aldehyde dehydrogenase activity is very low in the neuroblastoma tumors and in the cultured neuroblastoma cells. The generation of aldehydes and alcohols by the action of monoamine oxidase suggests that the deaminated metabolites of biogenic amines might exhibit some toxic effects in neuroblastoma patients.

CHANGES IN CATECHOLAMINE SYNTHESIZING ENZYME ACTIVITIES DURING NEURONAL GROWTH AND DEGENERATION

SUMMARY Dopamine-β-hydroxylase activity was used as a marker for neuroblastoma tumor growth. The increase in enzyme activity in the tumor and in the serum of mice that bear the tumor is proportional to the increase in size of the tumor. The removal of the tumor causes a marked decline in serum DβH activity. DβH activity in the cultured adrenergic cell line N-115-G of mouse neuroblastoma and in cultured cell line SK-N-SH of human neuroblastoma culture declines during early stages of growth while the total DβH activity increases. dB-cAMP causes a time-dependent increase in the specific activity of DβH. Changes in the specific DβH activity seem to be linked to changes in the cell morphology. Pharmacological and immunochemical studies indicate that a single enzyme catalyzes the decarboxylation of L-Dopa and L-5HTP in the striatum. The administration of 6-hydroxydopa causes a rise of DβH activity in the hypothalamus the first 2 days after treatment, and subsequently the enzyme activity falls below the control values. Two days after administration of 6-hydroxydopa, the enzyme activity in the brain stem decreases and remains below the control values on the eighth day posttreatment.