Interplay between aggression,brain monoamines and fur color mutation in the American mink

Domestication of wild animals alters the aggression towards humans, brain monoamines and coat pigmentation. Our aim is the interplay between aggression, brain monoamines and depigmentation. The Hedlund white mutation in the American mink is an extreme case of depigmentation observed in domesticated animals. The aggressive (?2.06 ± 0.03) and tame (+3.5 ± 0.1) populations of wild‐type dark brown color (standard) minks were bred during 17 successive generations for aggressive or tame reaction towards humans, respectively. The Hedlund mutation was transferred to the aggressive and tame backgrounds to generate aggressive (?1.2 ± 0.1) and tame (+3.0 ± 0.2) Hedlund minks. Four groups of 10 males with equal expression of aggressive (?2) or tame (+5) behavior, standard or with the Hedlund mutation, were selected to study biogenic amines in the brain. Decreased levels of noradrenaline in the hypothalamus, but increased concentrations of the serotonin metabolite, 5‐hydroxyindoleacetic acid and dopamine metabolite, homovanillic acid, in the striatum were measured in the tame compared with the aggressive standard minks. The Hedlund mutation increased noradrenaline level in the hypothalamus and substantia nigra, serotonin level in the substantia nigra and striatum and decreased dopamine concentration in the hypothalamus and striatum. Significant interaction effects were found between the Hedlund mutation and aggressive behavior on serotonin metabolism in the substantia nigra (P < 0.001), dopamine level in the midbrain (P < 0.01) and its metabolism in the striatum (P < 0.05). These results provide the first experimental evidence of the interplay between aggression, brain monoamines and the Hedlund mutation in the American minks.     

The brain catecholamines during domestication of the silver fox Vulpes fulvus

Studies have been made on the content of catecholamines (noradrenaline and dopamine) as well as metabolites of dopamine (3,4-dihydroxyphenylacetic and homovanillic acids) in the brain structures of silver foxes which differ in their handling reactions. The level of noradrenaline was found to be significantly higher in the anterior hypothalamus of domesticated animals; no differences in noradrenaline content were found in the frontal cortex, hippocamp, posterior hypothalamus and midbrain in animals from aggressive and domesticated groups. Dopamine content was higher in the tuberculum olfactorium of domesticated animals, being lower in the striatum and n. accumbens. Metabolite level remained unaffected which is presumably due to changes in dopamine synthesis in the investigated structures. It was concluded that domestication of animals favours the specimens with an altered state of catecholaminergic system of the brain.     

Change in certain forms of aggressive behavior and the concentration of monoamines in the brain during selection of wild rats for taming

Norway rats have been selected during 20 generations by the absence of aggressive reaction to man (tamed rats). From 7 up to 20th generations of selection, different forms of aggressive behaviour (reaction to glove, intermale, shock-induced aggression and predatory aggression) were studied, and the level of noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid was determined in the brain. In the absence of aggressive reaction to glove in tamed rats, the shock-induced aggression considerably decreased while the predatory aggressiveness (mouse-killing behaviour) and intermale aggressiveness did not change. Beginning from 15-16th generation of selection, a higher level of the 5-hydroxyindoleacetic acid in the hypothalamus was established, in the 20th generation an increased content of serotonin was revealed in the hypothalamus and the midbrain. In some generations of selection an increased level of noradrenaline in the hypothalamus in comparison to wild rats was observed. A conclusion is made that the selection of animals by taming unequally influences different kinds of aggressiveness and is accompanied by inherited consolidated reorganization of the monoamine brain systems.     

Dose-related effects of cysteamine treatment on hypothalamic and striatal dopamine, noradrenaline and serotonin neurotransmission

The dose-related effects of cysteamine treatment on hypothalamic and striatal neurotransmission were investigated. Cysteamine pretreatment with a dose of 150 mg/kg slightly increased the dopamine, and markedly decreased the noradrenaline, content of the hypothalamus in a dose-related manner. The serotonin levels of the hypothalamus and striatum were not affected. Cysteamine pretreatment with a higher dose (300 mg/kg sc) slightly increased the uptake of noradrenaline into hypothalamic slices. The drug did not influence dopamine and serotonin uptake into hypothalamus and striatal slices. These results suggest that cysteamine decreases rather selectively the noradrenaline content of the hypothalamus.     

Determination of monoamines and both forms of monoamine oxidase in the rat's substantia nigra during postnatal development

Changes in biogenic amine content in the substantia nigra and in both forms of monoamine oxidase in substantia nigra and striatum of the rat during postnatal development (15-180 days) have been studied. Dopamine and serotonin had the same levels at day 15, however, each monoamine showed a different developmental profile. Dopamine levels and their metabolites (except 3-methoxytyramine) decreased during postnatal development. Serotonin levels and their main metabolite, 5-hydroxyindolacetic acid, underwent an increase during all stages studied. There were no statistically significant changes in noradrenaline levels until day 180 when they increased with respect to day 15. The highest activity of the monoamine oxidase-A in substantia nigra coincided with the highest 5-hydroxyindolacetic acid:serotonin ratio. Monoamine oxidase-A in the striatum did not change contrary to that which happened in substantia nigra. The monoamine oxidase-B:monoamine oxidase-A ratio increased during development both in the substantia nigra and the striatum. The significance of these changes is discussed.     

Brain monoamines are involved in mediating the action of neurohypophyseal peptide hormones on ethanol tolerance

Two doses (0.3 and 3 ng peptide/animal) of oxytocin (OXT) and lysine-8-vasopressin (LVP) were earlier found to inhibit the development of tolerance to the hypothermic effect of ethanol in mice upon icv. administration. In the present paper the possible central monoaminergic correlates of the behavioral data were investigated. In tolerant animals the steady-state level of noradrenaline (NA) was increased in the hypothalamus, as was that of dopamine (DA) in the medulla oblongata; the serotonin (5-HT) and DA levels were decreased in the striatum as compared to those in the non-tolerant control. In the peptide-pretreated animals the NA level was increased in the hypothalamus, the DA level in the striatum, and the 5-HT level in the hippocampus and striatum. Opposite changes were observed in the steady-state levels of the monoamines in the hippocampus and striatum as compared to those in the tolerant controls. The data suggest that the central monoamines may be involved in mediating the actions of neurohypophyseal peptides on ethanol tolerance.     

Effect of neurotransplantation on the content of catecholamines in the rat brain structures after heavy craniocerebral trauma

It was found that heavy craniocerebral trauma (CCT) in rats results in a drop in the dopamine and noradrenaline content in the damaged cerebral hemisphere, striatum, and hypothalamus. Transplantation of embryonic neural tissue after CCT in rats favors restoration of the level of catecholamines. Thirty days after the transplantation, the level of noradrenaline and dopamine in damaged structures mentioned above becomes similar to that in intact animals, or exhibits a tendency to be restored.     

Effects of monorecessive and double recessive mutations affecting coat color on the monoamine content of the brain of the American mink (<Emphasis Type="Italic">Mustela vison</Emphasis> Schreber, 1777)

The effects of mutations affecting the coat color on the dopamine, noradrenaline, and serotonin contents of the hypothalamus and brainstem of the American mink have been studied. The sample comprised standard (+/+) and mutant minks, including the monorecessive pastel (b/b), silver-blue (p/p), and white hedlund (h/h) and the combination double recessive sapphire (a/a p/p) and pearl (k/k p/p) ones. The dopamine content of the brainstem of the monorecessive pastel (b/b) and silver-blue (p/p) minks has been found to be higher than in standard (+/+) minks. Conversely, the homozigosity for two coat color loci in double recessive pearl minks (k/k p/p) significantly decreases the noradrenaline and serotonin contents of the hypothalamus. In addition, monorecessive and double recessive minks differ from each other in the serotonin contents of the midbrain and medulla.     

EFFECTS OF AMINO-OXYACETIC ACID, ETHANOLAMINE-O-SULPHATE AND GABA ON THE CONTENTS OF GABA AND VARIOUS AMINES IN BRAIN SLICES

—The effects of amino-oxyacetic acid, ethanolamine-O-sulphate and γ-aminobutyric acid (GABA) on the contents of GABA, noradrenaline, dopamine and serotonin (5-HT) in slices of rat hypothalamus and midbrain were studied in vitro using a simultaneous fluorimetric assay procedure. Following control incubations the levels of 5-HT were raised, while the levels of the other substances remained steady. Amino-oxyacetic acid caused a reduction in the contents of noradrenaline and 5-HT, but had no effect on either GABA or dopamine. Ethanolamine-O-sulphate both raised the GABA content and lowered the noradrenaline content of slices, while the levels of dopamine and 5-HT were not altered. The presence of GABA in the incubation medium produced complex changes in these levels, depending both on the dose of GABA used and the brain area studied. In the hypothalamus, 0·07 mm -GABA caused an elevation in 5-HT, a drop in noradrenaline, and no change in either GABA or dopamine. With 5 mm -GABA, the noradrenaline level was raised slightly above control values and the endogenous GABA level doubled, while 5-HT and dopamine levels were not different from controls. Similar changes in 5-HT and GABA contents were observed with midbrain slices, but noradrenaline and dopamine were not affected. The possible modes of action of amino-oxyacetic acid and ethanolamine-O-sulphate on the amino acid and amine systems in the brain are discussed.     

Effects of an N-methyl-d-aspartate receptor agonist and its antagonist CPP on the levels of dopamine and serotonin metabolites in rat striatum collected in vivo by using a brain dialysis technique

3-((±)-2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) is an antagonist at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. In the present study, levels of dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) were measured after intracerebroventricular injection of NMDA, CPP or both in rat striatum using a brain dialysis method. The injection of NMDA produced a significant increase in DOPAC level. HVA level was also increased by NMDA injection. The level of 5-HIAA was not affected by NMDA injection. The injection of CPP had no effect on DOPAC, HVA and 5-HIAA levels. The injection of CPP restrained the increase of DOPAC and HVA levels induced by NMDA injection. The results suggest that intracerebral injection of NMDA may increase dopamine release from rat striatum, but have no effect on serotonin release. Furthermore, CPP inhibits NMDA induced release of dopamine.     

Low Selenium Diet Affects Monoamine Turnover Differentially in Substantia Nigra and Striatum

Abstract: Turnover of dopamine, noradrenaline. serotonin, and their metabolites has been measured in striatum and substantia nigra of adult female rats that were fed control or selenium-deficient diets for 15 days. In addition, the glutathione peroxidase activity has been studied. The most striking result was the increase of dopamine turnover (63%) and 3- methoxytyramine turnover (55%) in substantia nigra between control and experimental animals. On the other hand, no changes were found in the turnover rate of dopamine and its metabolites in the striatum. Likewise, no changes were found in noradrenaline turnover in substantia nigra. In the striatum, there was a significant increase of serotonin turnover versus no change for 5-hydroxy-3-indoleacetic acid. However, in the substantia nigra, serotonin turnover did not show significant changes, whereas 5-hydroxy-3-indoleacetic acid turnover decreased. At the same time, glutathione peroxidase activity significantly decreased in both structures after selenium-deficient diets. These results suggest that a selenium-deficient diet for a short period of time decreases brain protection. principally in the substantia nigra, against oxidative damage.     

Effect of Long-Lasting Diabetes Mellitus on Rat and Human Brain Monoamines

Experimental alloxan- or streptozotocin-produced diabetes in rats was accompanied by an increase in the levels of norepinephrine, dopamine, and serotonin, whereas the contents of metabolites, i.e., 5-hydroxyindoleacetic acid and homovanillic acid, in the whole brain gradually decreased with the duration of diabetes. Among the striatum, thalamus, and hypothalamus of alloxan diabetic rats, monoamine alterations were observed only in the hypothalamus; after 1 week an increase of norepinephrine content and after 13 weeks an increase of norepinephrine and dopamine contents were found. Tissues of 11 brain regions of 10 diabetic and 12 control patients post mortem were investigated for monoamine concentrations. Patients were all male, of similar age and interval between death and autopsy. Diabetic patients had an increase in the content of serotonin in the medial and lateral hypothalamus. The content of dopamine increased in the medial hypothalamus, putamen, and medial and lateral pallidus. In diabetic patients, the content of norepinephrine increased in the lateral pallidus and decreased in the nucleus accumbens and claustrum. Thus, it seems that diabetes mellitus in rats, as well as in humans is associated with regionally specific changes in brain monoamines.     

Diurnal patterns in brain biogenic amines of rats exposed to 60-Hz electric fields

Levels of brain neurotransmitters and their metabolites, as well as concentrations of enzymes associated with their synthesis and metabolism, fluctuate during the day in patterns defined as circadian. The present study examined these rhythms in albino rats exposed to 60-Hz electric fields. Thirty-six animals were exposed to a 39 kV/m field for 4 weeks, 20 h/day, in a parallel-plate electrode system. A group of 36 sham animals was similarly handled and housed in a nonenergized exposure system. On the sampling day, animals were sacrificed at 4-h intervals throughout the 24-h day. Brains were removed, dissected, and kept frozen until chemically analyzed. The levels of biogenic amines and their acidic metabolites in the striatum, hypothalamus, and hippocampus were determined by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) methods. Repeated exposure to 60-Hz electric fields produced significant alterations in the diurnal rhythms of several biogenic amines: dihydroxyphenylacetic acid (DOPAC, the primary metabolite of dopamine in the rat) in the striatum, and norepinephrine, dopamine, and 5-hydroxyindoleacetic acid (5-HIAA; serotonin metabolite) in the hypothalamus. Levels of serotonin in the striatum and hypothalamus showed clear circadian patterns that was not affected by the field. No diurnal or field-related changes were observed in the hippocampal amines.     

The effect of cocaine treatment on the level of dopamine and serotonin regeneration and on the level of acetylcholine in rat brain]

Cocaine treatment (10 or 50 mg/kg, i.m.): 1) did not change significantly the amount of 3H dopamine synthesized from 3H tyrosine in the striatum but reduced the specific activity of 3H tyrosine; 2) delayed the release of cerebral dopamine after inhibition of its biosynthesis by alpha-methylparatyrosine; 3) reduced the amount of 5-hydroxyindolacetic acid accumulated after Probenecid, which reflects an inhibitory effect on serotonin release; 4) did not change significantly the acetylcholine level of the brain.     

The activity of the monoaminergic systems of the rat hypothalamus in acute stress after chronic stressing]

The influence of chronic stress (footshock combined with randomized light flashes) on acute stress-induced (immobilization) release of noradrenaline, dopamine and serotonin in rat lateral hypothalamus was assessed by microdialysis. The chronic stress resulted in an increase and prolongation of the acute stress-induced release of noradrenaline but not of dopamine and serotonin. The increased rate of accumulation of dioxyphenylacetic acid and unchanged accumulation of homovanillic acid (dopamine metabolites) and dopamine during and after the acute stress in chronically stressed animals reflect a rise of synthetic activity of catecholaminergic systems in response to acute stress and reuptake increase. Marked stress-induced increase in hydroxyindoleacetic acid in chronically stressed rats without any changes in the ST dynamics may be regarded in a similar way. A significant increase in potassium-stimulated release of all the studied monoamines was found while their basal level remained unchanged. The conclusions was made that the hyperergic release of neurotransmitters may be the basis of an inadequate response of animals to acute stress, i.e., one of the neurotic symptoms.     

Post-mortem changes of neurotransmitter concentrations in the rat brain regions

Using High Performance Liquid Chromatography coupled with electrochemical detection the post-mortem stability of noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5-hydroxy indole acetic acid (5-HIAA) were examined in the rat hypothalamus, amygdala, cerebral cortex, cerebellum and corpus striatum over an 8 hour time period. Changes in concentrations of the different neurotransmitters were less than it might be expected. The significant changes were: a. A fall in NA levels in the cerebral cortex by 4 hours and in the hypothalamus at 8 hours. b. A reduction in DA concentrations in the corpus striatum at 8 hours but a two fold rise of levels in the hypothalamus at 1 and 2 hours. c. A four-fold increase in 5-HT concentrations in the amygdala throughout the 8 hours studied. The results indicate that for comparative studies on post-mortem brain tissue correction factors should be employed to take into account differential changes in the concentrations of the various neurotransmitters.     

Changes in biogenic amines in rat hippocampus during development and aging

The effects of postnatal development and aging on the concentration of dopamine, noradrenaline, serotonin and their principle metabolites have been studied in the hippocampus of the rat. During development the concentration of dopamine increases 1.5 fold during the first 90 days. 3-methoxytyramine was found in low concentrations. The homovanillic acid and DOPAC concentrations showed no changes apart from a decrease at day 15 and an increase at day 8, respectively. From birth up to 30 months, the noradrenaline concentration increased by a factor of about 10. Their metabolites each showed a different profile. The concentration of tryptophan was always the highest among the compounds studied. It decreased from birth to day 15, while the concentration of serotonin and 5-hydroxyindolacetic acid increased 3 and 5 fold respectively during this time. However, 5-hydroxytryptophan and 5-hydroxytryptophol concentrations were very low and unchanged at all stages. These findings led to the conclusion that the neurotransmitters: noradrenaline and serotonin, are developed in the hippocampus during the first three months. During aging, the serotonin concentration is increased without significant change in the other compounds studied.     

Brain tyrosine hydroxylase activity in behavior-selected silver foxes

In two groups of silver foxes--i.e. selected by the domestic type of behaviour and aggressive ones--studies have been made on the activity of the key enzyme in biosynthesis of catecholamines--i.e. tyrosine hydroxylase from the brain. Domesticated animals exhibited higher enzymic activity in the locus coeruleus, hypothalamus and cortex. Animals from both groups did not differ with respect to the level of tyrosine hydroxylase activity in the corpus striatum. The enzymic reactions of homogenates from locus coeruleus region of the brain in both groups of animals, as well as homogenates from the corpus striatum of the brain of aggressive animals exhibited low and approximately equal values of Michaelis constant for tyrosine. The value of KM was 3 times higher in the hypothalamus in both groups of foxes and in the corpus striatum of tame animals. Presumably, selection of silver foxes for the domestic type of behaviour resulted in the increase of biosynthesis of catecholamines in the brain due to the increase in the number of enzyme molecules. The increase in the activity of tyrosine hydroxylase in noradrenaline system of the brain may be associated with changes in the behavioural pattern of animals resulting from selection.     

Effects of long-term recovery from transient cerebral ischemia in rat brain: Tissue levels of acetylcholine,monoamines, and their metabolites

Concentrations of acetylcholine and the monoaminergic neurotransmitters dopamine, serotonin and their respective metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxyphenylacetic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA) and choline were simultaneously determined in the corpus striatum of rats after 15 min. complete cerebral ischemia (CCI) and in different intervals (1, 24, 48, 72, 96 hours) of postischemic cerebral reperfusion. Results were compared to respective sham-operated control animals. After 15 min. CCI acetylcholine concentration decreased to 15%, and dopamine concentration to 56% of the control values. The metabolite levels of DOPAC decreased to 40% and HVA to 64% of the control values. Acetylcholine, dopamine, serotonin and choline concentrations were not changed significantly after reperfusion. The metabolites HVA and 5-HIAA showed their maximum increases after 1 and 24 hours of reperfusion, additionally HVA was decreased both, after 72 and 96 hours of reperfusion. The data indicate that surprisingly little permanent damage could be caused by a 15 min. ischemia in the striatum. Tissue levels of the neurotransmitters appeared differentially altered but similarly regulated during ischemia and subsequent recirculation. Acetylcholine and dopamin levels decreased profoundly during ischemia. However, acetylcholine levels could be compensated rapidly during reperfusion, whereas the dopaminergic system showed a long-lasting change in its turnover rate. Although serotonin levels were unaffected by CCI, there was an increase of its presumed turnover rate during reperfusion.     

Brain Monoamine Changes in Rats After Short Periods of Ozone Exposure

We have shown in our laboratory that cat's and rat's sleep disturbances are produced by 24 h of ozone (O₃) exposure, indicating that the central nervous system is affected by this gas. To demonstrate the probable changes in brain neurotransmitters, we evaluated the monoamine contents of the midbrain and striatum of rats exposed to 1 part per million O₃ for 1 or 3 hours periods. The results were compared with rats exposed to fresh air and to those exposed to 3 hours of O₃ followed by 1 or 3 hours of fresh air. We found a significant increase in dopamine (DA) and its metabolites noradrenaline (NA) and 3,4 dihydroxyphenylacetic acid (DOPAC), as well as an increase in the 5-hydroxyindolacetic acid (5-HIAA) contents of the striatum. There were no changes in homovanillic acid (HVA) and serotonin (5-HT) levels during O₃ exposure. Additionally, an increase in DA, NA and 5-HIAA in the midbrain during O₃ exposure was observed. Turnover analysis revealed that DA increased more than its metabolites in both the midbrain and striatum. However, the metabolite of 5-HT, i.e. 5-HIAA, increased more than its precursor, this reaching statistical significance only in the midbrain. These findings demonstrate that O₃ or its reaction products affect the metabolism of major neurotransmitter systems as rapidly as after 1 h of exposition.