Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia

Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease.

The role of monoamines and acetylcholine-containing neurons in the regulation of the sleep-waking cycle

The Dopamine Hypothesis of Schizophrenia: A Review*

The levels of dopamine and norepinephrine were determined in the brains of fetal and newborn rats by means of a sensitive, radiometric-enzymatic assay. Catecholamines were converted to their 3-O-methylated derivatives in the presence of catechol-O-methyl transferase (EC 2.1.1.1) and [3 H-methyl]S-adenosylmethionine; and the [3H]-derivatives were isolated by selective extraction. The assay had a sensitivity for dopamine and norepinephrine of 100 picograms and was linear to at least 30 nanograms of catecholamines. Both amines were present at 15 days of gestation and increased 15-fold in content during the last week of gestation. The regional distribution of these neurotransmitters in the brain of the newborn rat correlated with the distribution of their biosynthetic enzymes. An investigation of the effects of reserpine, pheniprazine, α-methyl-para-tyrosine, diethyldithiocarbamate and l -DOPA on the levels of dopamine and norepinephrine in the brains of the 18-day gestational fetus indicated that the levels of these neurotransmitters are under controls similar to those known to occur in the brain of the adult rat.

Catecholamines in fetal and newborn rat brain.

1. After intracisternal administration, 6-hydroxydopamine had a greater effect on brain noradrenaline than on dopamine.2. Administration of two doses of 6-hydroxydopamine increased the depletion of noradrenaline but not of dopamine.3. Small doses of 6-hydroxydopamine decreased the concentration of noradrenaline with little or no effect on dopamine. Tyrosine hydroxylase activity was not reduced with these treatments.4. While pargyline pretreatment offered no advantage in the depletion of brain noradrenaline after 6-hydroxydopamine, depletion of brain dopamine was greatly potentiated by this treatment. The reduction of striatal tyrosine hydroxylase activity observed after 6-hydroxydopamine was also potentiated by pargyline pretreatment.5. The amounts of labelled noradrenaline and dopamine formed from (3)H-tyrosine were greatly reduced by 6-hydroxydopamine treatment. After (3)H-DOPA, formation of noradrenaline was greatly reduced while formation of labelled dopamine was only moderately reduced suggesting that decarboxylation of DOPA can occur in other than catecholamine containing neurones.6. Desmethylimipramine and imipramine inhibited depletion of noradrenaline produced by 6-hydroxydopamine but did not alter depletion of dopamine. Reserpine did not inhibit depletion of catecholamines produced by 6-hydroxydopamine.7. Administration of 6-hydroxydopamine to developing rats lowered both noradrenaline and dopamine concentrations as well as the tyrosine hydroxylase activity in the brains of these animals.

https://cdr.lib.unc.edu/downloads/1544br40k

Depletion of brain noradrenaline and dopamine by 6‐hydroxydopamine

After the intracisternal administration of 6-hydroxydopamine, brain levels of norepinephrine were reduced significantly with or without pargyline pretreatment. Depletion of dopamine in the central nervous system was found to be enhanced markedly by pargyline administration at higher dose levels of 6-hydroxydopamine. Brain serotonin concentrations were not altered. The effects of 6-hydroxydopamine were long-lasting with the depletion of brain amines persisting at 78 days. After norepinephrine-H3 intracisternally to animals treated with 6-hydroxydopamine, labeled norepinephrine uptake was diminished with a corresponding reduction of deaminated catechols and a marked increased in methylated amines. Tyrosine hydroxylase activity was found to be reduced in brainstem, caudate nucleus and whole brain in 6-hydroxydopamine-treated animals. Conversion of tyrosine-H3 to labeled norepinephrine and dopamine was also markedly diminished. The results support the view that 6-hydroxydopamine produces a “central sympathectomy” when introduced into cerebrospinal fluid.

https://cdr.lib.unc.edu/downloads/5h73pz00k

Effect of 6-hydroxydopamine on brain norepinephrine and dopamine: evidence for selective degeneration of catecholamine neurons

Summary

1
Brain noradrenaline, dopamine and tyrosine hydroxylase were found in rat brain a few days before birth and increased progressively until reaching adult values. The most rapid period of growth for these substances seemed to occur between 7 and 18 days.

2
The intracisternal administration of 6-hydroxydopamine to rats 7 days of age reduced concentrations of noradrenaline, dopamine, and tyrosine hydroxylase by 72 hours.

3
The concentrations of noradrenaline, dopamine or tyrosine hydroxylase in rats that received 6-hydroxydopamine at 7 or 14 days of age remained markedly reduced when determined at adulthood, indicating that fibres did not continue to develop after the administration of this compound. The rats treated at 7 days also showed diminished concentrations of noradrenaline in heart.

4
Rats injected with 6-hydroxydopamine at 7 days had reduced body weight as well as a reduction of some organ weights. This growth deficit was not observed in animals that received this drug at 14 days of age.

5
The administration of ovine growth hormone to rats that received 6-hydroxydopamine at 7 days did not reverse the growth deficiency in these animals.

/pdf/developmental-characteristics-of-brain-catecholamines-and-2zeyo7zkle.pdf

T. D. Traylor

Papers

Depletion of brain noradrenaline and dopamine by 6‐hydroxydopamine

Effect of 6-hydroxydopamine on brain norepinephrine and dopamine: evidence for selective degeneration of catecholamine neurons

Developmental characteristics of brain catecholamines and tyrosine hydroxylase in the rat: effects of 6‐hydroxydopamine