Brain Monoaminergic Activity Research Articles

P.5.002 Taurine in health care; in and off smoking and beyond

In female mammals, the postpartum period involves dramatic shifts in many socioemotional behaviors. This includes a suppression of anxiety-related behaviors that requires recent physical contact with offspring. Factors contributing to differences among females in their susceptibility to the anxiety-modulating effect of offspring contact are unknown, but could include their innate anxiety and brain monoaminergic activity. Anxiety behavior was assessed in a large group of nulliparous female rats and the least-anxious and most-anxious tertiles were mated. Anxiety was assessed again postpartum after females were permitted or prevented from contacting their offspring 4 h before testing. Levels of dopamine β-hydroxylase (DBH, norepinephrine synthesizing enzyme) and tryptophan hydroxylase-2 (TPH2, serotonin synthesizing enzyme) were measured in the brainstem and dorsal raphe, respectively. It was found that anxiety-related behavior in the two groups did not differ when dams were permitted contact with offspring before testing. Removal of the offspring before testing, however, differentially affected anxiety based on dams’ innate anxiety. Specifically, dams reverted back to their pre-mating levels of anxiety such that offspring removal slightly increased anxiety in the most-anxious females but greatly lowered anxiety in the least-anxious females. This reduction in anxiety in the least-anxious females after litter removal was associated with lower brainstem DBH. There was no relationship between females’ anxiety and dorsal raphe TPH2. Thus, a primary effect of recent contact with offspring on anxiety-related behavior in postpartum rats is to shift females away from their innate anxiety to a more moderate level of responding. This effect is particularly true for females with the lowest anxiety, may be mediated by central noradrenergic systems, and has implications for their ability to attend to their offspring.

Avoidance behavior and brain monoamines in fish

The crucian carp performs a typical avoidance behavior when exposed to olfactory cues from injured skin of conspecifics. They swim rapidly to the bottom and hide in available material. This work examines the effects of skin extract exposure and availability of hiding material on this behavior, and concomitant changes in brain monoaminergic activity in crucian carp. Individual fish were exposed to skin extract in aquaria with or without hiding material. Exposure to skin extract resulted in the expected avoidance behavior consisting of rapid movement towards the bottom of the aquarium. This lasted for 1–2 min. Activity then decreased below the level observed before exposure, suggesting a “freezing” type of avoidance behavior. This behavior was independent of availability of hiding material. Brain dopaminergic activity increased in telencephalon and decreased in the brain stem following skin extract exposure, again independent of availability of hiding material. However, fish kept in aquaria without hiding material showed an elevation of serotonergic activity in the brain stem and the optic tectum compared to fish with available hiding material. Absence of hiding material increased serotonergic activity also without exposure to skin extract. In aquaria with hiding material, the fish stirred up a cloud of fine sediments and showed a more pronounced decrease in locomotor activity in agreement with this being a more efficient freezing or immobile avoidance behavior. These results show that basic components of avoidance behavior and related brain changes are present in the fish brain, in accordance with the common phylogenetic roots of avoidance behavior in all vertebrates.

Changes in the Expression of Monoaminergic Genes under the Influence of Repeated Experience of Agonistic Interactions: From Behavior to Gene

The role of genetic and environmental factors as well as brain neurochemistry in regulating aggressive and submissive behaviors in animals are considered. We present a review of data on changes in brain monoaminergic activity (synthesis, catabolism, receptors) and on the expression of monoaminergetic genes under repeated daily agonistic confrontations in male mice. A repeated experience of aggression was shown to result in the total activation of the dopaminergic system and the inhibition of the serotonergic one. This was accompanied by a decrease in the mRNA level of the catechol-O-methyltransferase gene in the midbrain and an increase of the mRNA level of the dopamine transporter and tyrosine hydroxylase genes in the ventral tegmental area of aggressive male mice. Repeated experience of social defeats produced dynamic changes in the serotonergic system of some brain areas and an increase of the mRNA level of the serotonin transporter and monoamine oxidase A genes in the midbrain raphe nuclei. Theoretical and methodological possibilities of the proposed ethological approach for studying molecular mechanisms of agonistic behavior are discussed in the context of the fundamental problem of investigating the ways of regulation from behavior to gene.

Alterations of dopaminergic and serotonergic activity in the brain of sea-run Baltic salmon suffering a thiamine deficiency-related disorder

Baltic salmon Salmo salar females displaying wiggling behaviour had significantly lower (P<0.05) hepatic and ovarian thiamine (vitamin B1) concentrations than the normal females, confirming that they suffered from a thiamine deficiency. A significantly (P<0.05) increased monoaminergic activity was found in the telencephalon and the hypothalamus of the wiggling individuals as indicated by [5-hydroxyindoleacetic acid (5-HIAA)]: [5-hydroxytryptamine (5-HT)] and [3,4-dihydroxyphenylacetic acid (DOPAC)]: [dopamine (DA)] ratios. The 5-HIAA concentrations of wiggling individuals were significantly (P<0.05) higher in the telencephalon and the hypothalamus compared to normal fish. Wiggling fish showed significantly (P<0.05) higher concentrations of the DA metabolite DOPAC in the hypothalamus and the brain stem compared to normal fish. Furthermore, the brain stem in wiggling fish contained significantly (P<0.05) less 5-HT than in normal individuals, which was also reflected in a significant (P<0.05) increase in the (5-HIAA): (5-HT) ratio. These results demonstrate an increased serotonergic and dopaminergic activity in wiggling compared to normal fish. The altered monoaminergic activity may be directly related to altered brain thiamine metabolism, but a general stress caused by thiamine deficiency and an inability to regulate swim bladder inflation may contribute. Furthermore, a changed brain monoaminergic activity may contribute to the behaviour characterizing wiggling fish.

Alterations of dopaminergic and serotonergic activity in the brain of sea‐run Baltic salmon suffering a thiamine deficiency‐related disorder

Baltic salmon Salmo salar females displaying wiggling behaviour had significantly lower (P&lt;0.05) hepatic and ovarian thiamine (vitamin B1) concentrations than the normal females, confirming that they suffered from a thiamine deficiency. A significantly (P&lt;0.05) increased monoaminergic activity was found in the telencephalon and the hypothalamus of the wiggling individuals as indicated by [5‐hydroxyindoleacetic acid (5‐HIAA)]: [5‐hydroxytryptamine (5‐HT)] and [3,4‐dihydroxyphenylacetic acid (DOPAC)]: [dopamine (DA)] ratios. The 5‐HIAA concentrations of wiggling individuals were significantly (P&lt;0.05) higher in the telencephalon and the hypothalamus compared to normal fish. Wiggling fish showed significantly (P&lt;0.05) higher concentrations of the DA metabolite DOPAC in the hypothalamus and the brain stem compared to normal fish. Furthermore, the brain stem in wiggling fish contained significantly (P&lt;0.05) less 5‐HT than in normal individuals, which was also reflected in a significant (P&lt;0.05) increase in the (5‐HIAA): (5‐HT) ratio. These results demonstrate an increased serotonergic and dopaminergic activity in wiggling compared to normal fish. The altered monoaminergic activity may be directly related to altered brain thiamine metabolism, but a general stress caused by thiamine deficiency and an inability to regulate swim bladder inflation may contribute. Furthermore, a changed brain monoaminergic activity may contribute to the behaviour characterizing wiggling fish.

Effects ofSchistocephalus solidusinfection on brain monoaminergic activity in female three-spined sticklebacksGasterosteus aculeatus

The three-spined stickleback Gasterosteus aculeatus is an intermediate host of the tapeworm Schistocephalus solidus. Changes in predator avoidance, foraging and shoaling behaviour have been reported in sticklebacks infested with S. solidus, but the mechanisms underlying parasite-induced behavioural changes are not understood. Monoamine neurotransmitters are involved in the control of behaviour and central monoaminergic systems are sensitive to various stressors. Thus, the behavioural effects of S. solidus infestation might be a reflection of changes in brain monoaminergic activity in the stickleback host. The concentrations of 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE) and their metabolites 5-hydroxy-indoleacetic acid (5-HIAA), homovanilic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in the telencephalons, hypothalami and brainstems of parasitized and non-parasitized female sticklebacks held in the laboratory. The ratios of 5-HIAA:5-HT were significantly elevated in both the hypothalami and brainstems of infected sticklebacks. The concentrations of 5-HT and NE were significantly reduced in the telencephalons of infected fish as compared with controls, but there was no elevation of metabolite concentrations. The results are consistent with chronic stress in infected fish, but may also reflect other alterations of neuroendocrine status resulting from parasite infection.

HTR2C Cys23Ser polymorphism in relation to CSF monoamine metabolite concentrations and DSM-III-R psychiatric diagnoses

Background: Heritable variation in brain monoaminergic activity has been suggested to lead to interindividual differences in vulnerability to alcoholism, and many other behavioral disorders. We evaluated if a functional Cys23Ser polymorphism in the 5–HT2C receptor gene, the principal serotonin receptor in the brain, contributes to variation in serotonin, norepinephrine and dopamine activity, as indexed by their major metabolite concentrations in cerebrospinal fluid (CSF). Genotype–monoamine metabolite concentration associations were subsequently correlated to risk for alcoholism. Methods: The study sample consisted of unrelated Finnish males, including 214 alcoholic, violent offenders and 222 population controls who were interviewed using the Structured Clinical Interview for DSM-III-R, blind rated for psychiatric diagnoses and typed for the HTR2C Cys23Ser polymorphism. CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), the major metabolite of norepinephrine, and homovanillic acid (HVA), the major metabolite of dopamine were available from 195 individuals. Results: The major finding in this study was that HTR2C CysSer23 significantly contributed to CSF MHPG concentrations ( p = .012). Higher concentrations of CSF MHPG were observed both in alcoholic violent offenders and population controls with HTR2C Ser23 genotype. Despite the association of Cys23Ser to CSF MHPG, HTR2C genotype was not associated with alcoholism, nor with other psychiatric disorders present in this sample. Conclusions: We conclude that a functional HTR2C Cys23Ser polymorphism contributes to the interindividual genetic variation of CSF MHPG explaining 3% of the total variance. This finding suggests that 5-HT2C receptors are involved in the regulation of norepinephrine turnover in humans; however, HTR2C Cys23Ser does not appear to contribute to the risk of alcoholism, or its contribution to this complex and heterogenous disorder is too small to be detected by a sample of this size and structure.

CSF Monoamines, Age and Impulsivity in Wild Grivet Monkeys (Cercopithecus aethiops aethiops)

Brain monoaminergic activity has been associated with behaviors, such as impulsive risk-taking, that tend to peak during adolescence in humans and nonhuman primates. This study was designed to assess natural variation in monoamine neurotransmitter metabolism in relation to age and behavioral impulsivity in grivet monkeys (Cercopithecus aethiops aethiops) living in their native habitat and subject to natural ecological pressures. Cisternal cerebrospinal fluid, collected from 22 animals living in the Awash National Park, Ethiopia, was assayed for the major metabolites of serotonin (5-hydroxyindoleacetic acid, 5-HIAA), dopamine (homovanillic acid, HVA) and norepinephrine (3-methoxy-4-hydroxyphenylglycol, MHPG). Concentrations of HVA declined significantly from one year of age to older adulthood. Further, a significant curvilinear relationship was identified between age and the 5-HIAA/HVA ratio, with the trough coinciding with the period of adolescence. Finally, behavioral impulsivity, as measured by re-entering baited traps a second time after the animal had already been captured and sampled for CSF, was related to lower levels of MHPG. The results suggest that normal variation in central monoaminergic activity may have functional consequences in wild populations.

Behavioral and physiological markers of experimental depression induced by social conflicts (DISC)

This paper summarizes data confirming the development of depression induced by so- cial conflicts (DISC) in male mice of C57BL/6J strain. Repeated defeat experiences in daily agonistic confrontations induced dramatic changes in behaviors as well as in the somatic state of submissive mice (losers) that were similar to symptoms of human de- pression with respect to etiology, susceptibility to treatment, and symptomatology. A remarkable behavioral deficit was found in losers, who demonstrated only a passive defense and immobile postures after 20 daily defeats (tests) instead of active defense and withdrawal, which had predominated in the first confrontations. Losers never demon- strated any aggression to other individuals and displayed a decrease in ambulation in the open-field test as well as an increase in immobility time in Porsolt's test. The devel- opment of anxiety and disturbance in communicative behavior were observed in losers. Loss of weight and enhancement of gastric mucosa damage, as well as a decrease in plasma testosterone level and immune resistance, were shown in losers. Chronic imi- pramine and tianeptine treatment prevented the increase of depressiveness as esti- mated by Porsolt's test. Chronic unavoidable social stress is considered a pathogenic factor, which leads to the development of depressive pathology and anxiety in mice. The study on brain monoaminergic activity in losers at different stages of the experimental depression allows the hypothesis that the development of depression is accompanied by dynamic changes in turnover and reception of at least brain serotonin, depending on the duration and depth of the pathological depressive processes. Behavioral and physiologi- cal markers of a depression-like state in losers are discussed in comparison with those of human depressive disorder. Aggr. Behav. 24:271-286, 1998. © 1998 Wiley-Liss, Inc.

Effect of social rank on brain monoaminergic activity in a cichlid fish.

In Haplochromis burtoni, an African cichlid fish, male sexual maturation is regulated via social interactions, and these effects are mediated by gonadotropin-releasing-hormone (GnRH)-containing neurons in the preoptic area of the brain. Since brain monoaminergic systems are known to be involved in the regulation of GnRH release, and the activity of these systems is influenced by agonistic interactions, we analyzed the effect of social status on brain monoaminergic activity in H. burtoni. Animals were either (1) in normal social groups consisting of two males and four females or (2) in groups of one male and five females. Quantitative behavioral observations were made on each group of animals and, following sacrifice several physiological measurements were made. Concentrations of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA, the main 5-HT metabolite) and tryptophan (TRP, the amino acid precursor of 5-HT), dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC, the main DA metabolite) were measured. The 5-HIAA/5-HT and DOPAC/DA ratios were calculated and used as indexes of 5-HT and DA activity, respectively. In addition, the gonadosomatic index was calculated from body and gonadal weights and used as an index of reproductive status. Concentrations of 5-HIAA as well as 5-HIAA/5-HT ratios were significantly higher in the brainstem of non-territorial males than in that of territorial males, and similar trends were seen in the telencephalon and hypothalamus. Moreover, TRP concentrations in the telencephalon and brainstem were significantly lower in non-territorial males. In this species, sexual maturation in females is not socially regulated, and there was no significant correlation between measured antagonistic behavior and biochemical indices. These results suggest a fundamental difference in the neurochemical responses between male and female H. burtoni.

The effects of two chronic intermittent stressors on brain monoamines

The effects of chronic exposure (27 days) to two different Stressors on brain monoaminergic activity was studied in adult male rats. The Stressors used were restraint in tubes (RES) and immobilization in wooden boards (IMO). Both chronically stressed and stress naive (control) rats were subjected to 0, 15, and 60 min of the same Stressor to which they were chronically exposed. Previous chronic exposure to either RES or IMO significantly reduced ACTH response to the same Stressor. Monoaminergic response to these Stressors was studied by measuring the levels of noradrenaline (NA), serotonin (5-HT) and their metabolites: 3-methoxy,4-hydroxyphenyletileneglycol sulfate (MHPG-SO 4) and 5-hydroxyindoleacetic acid (5-HIAA), respectively. The regions studied were: pons plus medulla, midbrain, hypothalamus, hippocampus, and frontal cortex. Previous chronic exposure to the Stressors induced only few changes in the resting levels of the monoamines and their metabolites. In addition, monoaminergic response to the same Stressor to which they were chronically exposed was always similar in control and chronically stressed rats. These data indicate that brain NA and 5-HT metabolism is less sensitive than ACTH to the process of habituation to a repeated Stressor, at least in the gross areas of the brain analyzed in the present study.

Reduced3H-Dopamine Uptake by Blood Platelets in Patients with Prolactin-Secreting Pituitary Adenoma

Uptake of 3H-Dopamine by blood platelets was found to be significantly reduced in eight patients with prolactin (PRL) secreting pituitary adenoma in comparison to normal subjects (27.91±5.01 nmol/1011 platelets vs. 73.42±4.99 nmol/1011 platelets, p<0.001). Since platelet monoamine uptake seems to reflect brain monoaminergic activity, the reduction of dopamine uptake (DAU) in our hyperprolactinemic subjects suggests a defective dopaminergic neurotransmission in patients with PRL-secreting tumors.