Monoamine neurotransmitters and their metabolites in the mature rabbit brain following induction of hydrocephalus.

Functional and behavioral disturbances associated with hydrocephalus may be due in part to altered neurotransmitter function in the brain. Hydrocephalus was induced in adult rabbits by injection of silicone oil into the cisterna magna. These and controls were killed 3 days, 1 and 4 weeks post-injection. Tissue concentrations of norepinephrine, epinephrine, serotonin, dopamine, and the metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were determined in fifteen brain regions using HPLC. There were decreases in hypothalamic and medullary dopamine, transient decreases in basal ganglia serotonin, increases in thalamic noradrenaline, and increases in hypothalamic and thalamic epinephrine. Changes in the primary neurotransmitters may be attributable to damage of their axonal projection systems. Metabolite concentrations increased in the cerebrum. Reduced clearance of extracellular fluid which accompanies cerebrospinal fluid stasis may explain the accumulation of metabolites.

Monoamine neurotransmitters and amino acids in the cerebrum and striatum of immature rats with kaolin-induced hydrocephalus.

Hydrocephalus is characterized by enlargement of the cerebral ventricles. The behavioral disturbances are, in some cases, rapidly reversible by surgical treatment suggesting that there may be a functional impairment of neurons. Hydrocephalus was induced in 3-week old rats by kaolin injection into the cisterna magna. Parietal cerebrum and striatum content of monoamine neurotransmitters and amino acids were assayed by high performance liquid chromatography (HPLC), 1, 2, or 4 weeks after induction of hydrocephalus. The ventricles exhibited progressive enlargement which was partially reversed by surgical treatment. Cerebral water content was increased at all stages. Increased levels of cerebral aspartate and glutamate suggest that there is the potential for excitatory neurotoxicity. The increase in cerebral taurine correlated negatively with the increase in water content. Cerebral concentrations of norepinephrine and serotonin, and its metabolite 5-HIAA, were increased at 1 and 2 weeks suggesting an increase in their turnover during the early stages of ventricular dilatation. Dopamine and its metabolite DOPAC were transiently diminished in the striatum at 1 and 2 weeks, respectively, suggesting that axonal projections from the brainstem may be impaired. We conclude that the effect of hydrocephalus on amino acids and monoamines varies regionally. Due to increased water content, there may be dilution effects in whole tissue, therefore, it is important to make determinations on the basis of protein content.

Effects of valproate on amino acid and monoamine concentrations in striatum of audiogenic seizure-prone Balb/c mice.

The effects of valproate on CNS concentrations of gamma-aminobutyric acid (GABA), glulamate (GLU), glutamine (GLN); dopamine (DA), serotonin (5-HT), and metabolites were examined in tissue extracts of caudate nucleus of genetic substrains of Balb/c mice susceptible (EP) or resistant (ER) to audiogenic seizures. Generalized tonic-clonic seizures observed in EP mice were inhibited by valproate, administered 1 h prior to testing, in a dose-response fashion. Concentrations of GABA, GLU, and GLN, which were lower in EP mice than in ER mice, were significantly increased by valproate at doses of 180 and 360 mg/kg. Concentrations of homovanillic acid (HVA) and hydroxyindoleacetic acid (5-HIAA), metabolites of DA and 5-HT, were substantially increased by valproate at these doses. The in situ activity of tyrosine hydroxylase (TH) was not significantly influenced by valproate, whereas a valproate-induced increase in tryptophan hydroxylase (TPH) activity was observed in both striatum and in midbrain tegmentum. The data are consistent with the interpretation that anti-convulsive doses of valproate influences the intraneuronal metabolism of monoamines, GABA, and glutamate concurrently. Valproate's influence on the metabolism of both major inhibitory (GABA) and excitatory (GLY amino acids in striatum could contribute to its anti-convulsive effects in genetically seizure prone mice, as well as to the accumulation of DA and 5-HT metabolites.

Melatonin reduces dopamine content in the neurointermediate lobe of male Syrian hamsters.

The effect of daily late afternoon administration of melatonin on the in situ activity of tyrosine hydroxylase (TH) was studied in the posterior pituitary (neurointermediate lobe) of the male Syrian hamster. After 3 weeks of melatonin administration, TH activity was significantly reduced in the posterior pituitary. This was associated with a significant decrease in norepinephrine (NE) content. After 5 weeks, TH activity and NE content were no longer significantly different from controls. Dopamine (DA) content of the posterior pituitary was decreased progressively by melatonin administration, with a reduction of greater than 50% after 5 weeks of treatment. These data provide evidence that melatonin has a potent inhibitory effect on the regulation of the dopaminergic system of the neurointermediate lobe--an effect that appears unrelated to changes in axonal TH.

Extrahypothalamic effects of melatonin administration on serotonin and norepinephrine synthesis in female Syrian hamsters.

The effects of daily late afternoon injections of melatonin for 10 weeks on the metabolism of serotonin (5-HT) and norepinephrine (NE) were examined in regional brain extracts of intact and ovariectomized (GX) Syrian hamsters. Accumulation of 5-HT and NE after administration of the monoamine oxidase inhibitor pargyline was used as a measure of the rate of neurotransmitter synthesis-with concentrations determined by HPLC with electrochemical detection. Daytime 5-HT synthesis was significantly decreased in the amygdala of melatonin-treated hamsters that had been GX (to 50% of GX controls). No significant effect on 5-HT synthesis could be detected in the mediobasal hypothalamus (MBH), however, a significant increase was demonstrated in the pontine brain stem of both intact and GX hamsters treated with melatonin. Daytime NE synthesis was decreased to levels not significantly different from zero in the amygdala of GX hamsters treated with melatonin, while in the brain stem, melatonin reduced NE synthesis in both intact and GX animals. The present data demonstrate that these melatonin effects on 5-HT and NE metabolism are not limited to the MBH and are not secondary to melatonin-induced changes in circulating levels of the ovarian steroids.