Effects of gonadectomy and sex hormones on the levels of noradrenaline and dopamine in rat hypothalamus

The levels of noradrenaline and dopamine were determined in the homogenates of the hypothalamus of rats of either sex. The determinations were done in intact rats, after sham gonadectomy, 6 and 9 weeks after gonadectomy, and in gonadectomized rats receiving 6 weeks after gonadectomy one dose of oestradiol cypionate (females) or testosterone cypionate (males). Catecholamines were determined fluorimetrically. The changes of the determined catecholamines differed in the hypothalamic homogenates in males and females after gonadectomy. Following orchidectomy the noradrenaline level rose, while after ovariectomy the level of this catecholamine decreased. Contrary to this, in ovariectomized rats the dopamine level was significantly raised after the operation. This change was reversible as observed after administration of oestradiol cypionate. Orchidectomy and testosterone cypionate injection had no effect on the dopamine level in the hypothalamus. The role of these catecholamines in the processes connected with the regulation of the hypothalamus-hypophysis-gonad axis is discussed.     

Sexually Dimorphic Effects of Catechol-O-Methyltransferase (COMT) Inhibition on Dopamine Metabolism in Multiple Brain Regions

The catechol-O-methyltransferase (COMT) enzyme metabolises catecholamines. COMT inhibitors are licensed for the adjunctive treatment of Parkinson''s disease and are attractive therapeutic candidates for other neuropsychiatric conditions. COMT regulates dopamine levels in the prefrontal cortex (PFC) but plays a lesser role in the striatum. However, its significance in other brain regions is largely unknown, despite its links with a broad range of behavioural phenotypes hinting at more widespread effects. Here, we investigated the effect of acute systemic administration of the brain-penetrant COMT inhibitor tolcapone on tissue levels of dopamine, noradrenaline, and the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). We examined PFC, striatum, hippocampus and cerebellum in the rat. We studied both males and females, given sexual dimorphisms in several aspects of COMT''s function. Compared with vehicle, tolcapone significantly increased dopamine levels in the ventral hippocampus, but did not affect dopamine in other regions, nor noradrenaline in any region investigated. Tolcapone increased DOPAC and/or decreased HVA in all brain regions studied. Notably, several of the changes in DOPAC and HVA, particularly those in PFC, were more prominent in females than males. These data demonstrate that COMT alters ventral hippocampal dopamine levels, as well as regulating dopamine metabolism in all brain regions studied. They demonstrate that COMT is of significance beyond the PFC, consistent with its links with a broad range of behavioural phenotypes. Furthermore, they suggest that the impact of tolcapone may be greater in females than males, a finding which may be of clinical significance in terms of the efficacy and dosing of COMT inhibitors.     

Dopamine levels in the mosquito Aedes aegypti during adult development, following blood feeding and in response to heat stress

Dopamine, a catecholamine neurotransmitter, is important for insect development and is known to be involved in insect stress responses. In the current study, dopamine was analysed in Aedes aegypti heads by HPLC. We found that immediately after adult emergence, males have significantly higher concentrations of dopamine than females, and that dopamine concentrations decrease with age in both sexes. Dopamine levels increase in females following a blood meal suggesting that dopamine might be involved in ovarian- and/or egg-development. We also found that female mosquitoes have a higher tolerance to a short term thermal stress in a water bath than males up to 44 degrees C, however, both sexes die if exposed to short term temperatures between 44 and 45 degrees C. Finally, we did not find any indication that dopamine levels were associated with short time thermal stress response in female mosquitoes.     

Catecholamines in regulation of development of GnRH neurons of rat fetuses

The contents of dopamine, serotonin, and noradrenaline in rat fetuses developing under the conditions of their deficiency induced by administration of alpha-methyl-para-tyrosine to females during 11th to 16th or 20th day of pregnancy and in fetuses, whose mothers were given saline at the same time, were determined using HPLC with subsequent electrochemical detection. Administration of alpha-methyl-para-tyrosine led to decreased levels of dopamine and noradrenaline in the areas of migration of GnRH-neurons in fetuses on days 17 and 21 of prenatal development. The concentration of serotonin remained unchanged, except in the head nasal area in males on day 21. The areas of interaction between the brain catecholaminergic systems and migrating and differentiating GnRH-neurons were determined by double immunohistochemical labeling. Close topographical location of GnRH-immunoreactive neurons and tyrosine hydroxylase-immunoreactive in the area of nucleus accumbens on days 17 and 20, as well as in the median eminence on day 20. The GnRH concentration in the caudal areas of migration of GnRH-neurons under the normal conditions and in the case of catecholamine deficiency was determined using radioimmunoassay. After administration of alpha-methyl-para-tyrosine the GnRH concentration in the anterior hypothalamus decreased in females. The data obtained suggest the involvement of catecholamines in the regulation of development of GnRH-Neurons during prenatal development. In addition, the adequacy and efficiency of the used model of catecholamine deficiency for studying the development of such neurons was confirmed.     

Effects of diet macronutrient composition on body composition and fat distribution during weight maintenance and weight loss

Objective: Neurotransmitter systems participate in the regulation of food intake, and their activities are expected to influence eating behavior. Design and Methods: We investigated possible associations between body mass index (BMI) and central noradrenaline, serotonin, and dopamine activities, as reflected by the cerebrospinal fluid levels of their main metabolites methoxyhydroxyphenylglycol (MHPG), 5‐hydroxyindoleacetic acid (5‐HIAA), and homovanillic acid (HVA), respectively. We studied 192 subjects (111 males, 81 females) admitted to neurologic clinic for diagnostic investigations that included CSF analysis, and were found not to suffer from any major neurological disease. Subjects were categorized in three groups, namely in lower, in the two middle, and in upper BMI quartiles, the limits calculated separately for males and females. Results: No differences were found in MHPG levels between groups, while subjects in the upper BMI quartile showed significantly elevated levels of 5‐HIAA and HVA compared to the levels of subjects in lower and middle quartiles. Conclusions: The results provide evidence that in overweight subjects there are enhanced demands in serotoninergic and dopaminergic signaling for their reward system that may lead to increased motivation for food consumption. The implication of reward centers in eating behavior supports the hypothesis of common mechanisms in obesity and drug addiction.     

Cerebrospinal Fluid Measurements Suggest Precursor Availability and Sex Are Involved in the Control of Biogenic Amine Metabolism in a Primate

Biogenic amine precursors and metabolites were measured in cisternal cerebrospinal fluid from 83 female and 55 male vervet monkeys. The results indicate that mean rates of 5-hydroxytryptamine, dopamine, and noradrenaline metabolism in the brain are higher in females than in males. They also suggest that under physiological circumstances tryptophan availability is involved in the control of brain 5-hydroxytryptamine synthesis while tyrosine availability is involved in control of both dopamine and noradrenaline metabolism. The similarities seen between our results on vervets and those seen with human cerebrospinal fluid suggest that the vervet is a useful primate to study.     

Catecholamines in Regulation of Development of GnRH Neurons of Rat Fetuses

The contents of dopamine, serotonin, and noradrenaline in rat fetuses developing under the conditions of their deficiency induced by administration of α-methyl-para-tyrosine to females during 11th to 16th or 20th day of pregnancy and in fetuses, whose mothers were given saline at the same time, were determined using HPLC with subsequent electrochemical detection. Administration of α-methyl-para-tyrosine led to decreased levels of dopamine and noradrenaline in the areas of migration of GnRH-neurons in fetuses on days 17 and 21 of prenatal development. The concentration of serotonin remained unchanged, except in the head nasal area in males on day 21. The areas of interaction between the brain catecholaminergic systems and migrating and differentiating GnRH-neurons were determined by double immunohistochemical labeling. Close topographical location of GnRH-immunoreactive neurons and tyrosine hydroxylase-immunoreactive in the area of nucleus accumbens on days 17 and 20, as well as in the median eminence on day 20. The GnRH concentration in the caudal areas of migration of GnRH-neurons under the normal conditions and in the case of catecholamine deficiency was determined using radioimmunoassay. After administration of α-methyl-para-tyrosine the GnRH concentration in the anterior hypothalamus decreased in females. The data obtained suggest the involvement of catecholamines in the regulation of development of GnRH-Neurons during prenatal development. In addition, the adequacy and efficiency of the used model of catecholamine deficiency for studying the development of such neurons was confirmed.     

The effects of adrenalectomy on the ontogenesis of brain: noradrenaline and dopamine content

The effect of adrenalectomy on catecholamine content in the diencephalon and the rest of the brain of male and female rats during the post-natal period was studied. Seven days after adrenalectomy, there is no change in noradrenaline or dopamine content. However, the dopamine levels of both the diencephalon and the rest of the brain decrease with age between days 45 and 60, while noradrenaline content in the diencephalon and the rest of the brain remained unchanged. Thus adrenalectomy significantly affected the developmental pattern of brain dopamine.     

Brain monoamines and sexual behavior in Japanese quail: Effects of castration and steroid replacement therapy

In the male Japanese quail, testosterone is required for the activation of sexual behavior. This steroid dependent process may rely heavily on mediation via monoaminergic neurons. These experiments were conducted to study the relationship between reproductive state (hormonal and behavioral components) and levels of monoamines in selected areas of the brain in Japanese quail. In Experiment 1, monoamine levels in a number of brain areas were compared in castrates, testosterone-implanted castrates, and intact males. Monoamine levels were comparable to those previously measured in Japanese quail, and there were no significant differences due to treatment. Plasma luteinizing hormone (LH) levels and recovery of cloacal gland area in implanted castrates confirmed the afficacy of treatments. In Experiment 2, the disappearance of dopamine (DA) and norepinephrine (NE) following administration of a-methyl-para-tyrosine (aMPT) was used as an indicator of turnover rate. Male and female quail were gonadectomized at 3 weeks of age. At the age of five weeks, some gonadectomized males and females were given implants containing testosterone. Only intact males and testosterone-implanted castrated males showed reproductive behavior. Plasma gonadotropin levels were elevated in gonadectomized birds and reduced in steroid-implanted gonadectomized birds. The aMPT treatment significantly reduced the levels of DA and NE in the telecephalon and the level of DA in the hypothalamus. After aMPT treatment, the disappearance of NE in the telecephalon and of DA in the hypothalamus were significantly different according to the sex or treatment of the birds or both. Significant interactions between these two factors were observed. Disappearance rate of NE in the telecephalon was decreased by castration of males and increased by ovariectomy of females. Both effects were counteracted by testosterone. Reverse effects were observed for DA disappearance in the hypothalamus (increase with castration in males and decrease with ovariectomy in females). These results give evidence for altered aminergic function in specific areas of the brain relative to altered reproductive state.     

Age- and gender-related changes in body size, adiposity, and endocrine and metabolic parameters in free-ranging rhesus macaques.

Normative age- and gender-related changes in body composition, serum lipids, testosterone, and insulin-like growth factor (IGF-1) were examined in the Cayo Santiago free-ranging rhesus macaques. In both adult males and females, body weights, crown-rump lengths, and circumference of the limbs were lowest in the oldest group (20+ years of age) as compared with other adult age classes. Body fat, as reflected in subcutaneous fatfold thickness and waist/thigh ratios, were higher in adult females than adult males. This gender dimorphism was first detectable among the 6-9 year old age group. Greatest body fat among females was observed in the 10-14 age group, whereas in males the highest values were observed in the 15-19 age group. Differences in body composition were also observed with respect to reproductive status. Although there were no gender differences in overall cholesterol levels, there were age-related differences between males and females, and only in males were cholesterol values positively related to adiposity. There were no age- or gender-related differences in triglyceride values, but levels were significantly higher in pregnant females in comparison with other reproductive states. Levels of testosterone were not significantly related to any morphometric parameter and values did not decrease significantly with age. Levels of IGF-1 exhibited a significant age-related decrease among adult males, and females had higher levels independent of age. The similarities between the present findings and human studies suggest that further studies in the free-ranging rhesus macaques would provide a bridge between studies of laboratory-housed primates and studies of human beings with respect to the etiology of obesity and life-history changes in body composition and endocrine and metabolic parameters.     

Growth differences and dimorphic expression of growth hormone (GH) in female and male Cynoglossus semilaevis after male sexual maturation

Half-smooth tongue sole, Cynoglossus semilaevis, is an ideal model to investigate the regulatory mechanisms of sexual growth dimorphism in fish species. The aim of the study was to investigate the effect of differential age of sexual maturity for females and males on growth and GH mRNA expression in C. semilaevis. The body weight differences between the sexes were not significant in C. semilaevis at age 5 months when females and males were all immature. Significant differences in body weight between the sexes were found after early sexual maturation of males at the age of 9 months. The body weight of 21-month-old females (621.4 ± 86.4g), still not immature, was even 3.28 times higher than that of the males (189.7 ± 14.4g). The cDNAs encoding GH in C. semilaevis was cloned. The GH gene is 2924bp long and consists of six exons and five introns. The results of qRT-PCR showed that GH mRNA levels of the immature females were not significantly different from that of immature males at age 5 months. However, GH mRNA levels of the immature females were significantly higher compared with those of the mature males at age 9 months (P<0.05). At age 11 months, GH mRNA levels of females were even 6.4-fold higher than that of males. In conclusion, for the first time we show that early sexual maturity of males is the main cause of sexual growth dimorphism in C. semilaevis and exert significant effect on GH mRNA expression.     

Release of dopamine, noradrenaline and dopamine B-hydroxylase from mouse neuroblastoma

The murine C1300 neuroblastoma tumor was found to secrete dopamine, noradrenaline and dopamine B-hydroxylase into the circulation of tumor-bearing A/J mice. The plasma levels of dopamine, noradrenaline and dopamine B-hydroxylase increased with the size of the tumor, and the increase in noradrenaline paralleled the increase in dopamine B-hydroxylase (r = 0.86). The vesicular storage of dopamine and noradrenaline in the tumor was evidenced by a decrease of the tissue content of dopamine and noradrenaline 24 hours after the administration of reserpine (5 micrograms/g) respectively to 17.6% and 7.8% of control values. A similar observation could be made for the levels of dopamine and noradrenaline in the plasma of reserpinized C1300 mice. The total activity of dopamine B-hydroxylase in the tumor and in plasma was unaffected by the reserpine treatment. Chronic administration of 6-hydroxydopamine (100 micrograms/g for 8 days) had no effect on the tissue contents of dopamine, noradrenaline or dopamine B-hydroxylase. The release of catecholamines and dopamine B-hydroxylase from the C1300 neuroblastoma was studied in vitro on superfused tumor slices. Stimulation of these slices with 56 mM KC1 or with 5.10(-5) M tyramine failed to induce the release of endogenous dopamine, noradrenaline or dopamine B-hydroxylase above the basal outflow levels. These results are suggestive for a non-exocytotic release of catecholamines and dopamine B-hydroxylase from the neuroblastoma tumor.     

Sex-related differences in free plasma catecholamines in individuals of similar performance ability during graded ergometric exercise

Sex-related differences of catecholamine responses were evaluated in nine healthy women and six age-matched men at rest and during incremental treadmill exercise. Heart rate, oxygen uptake (VO2), glucose and lactate blood levels as well as the free plasma catecholamines, noradrenaline and adrenaline, were determined. No significant differences were observed for these parameters between the two groups at rest. The females had relative VO2max and maximal running velocities similar to the males, which points to a comparable dynamic performance ability. However, at identical work loads, noradrenaline, adrenaline and glucose levels were significantly higher in women than in men. Lactate, heart rate and relative VO2 showed a similar tendency at submaximal exercise levels, indicating higher strain at identical stress levels in women. The reason for the higher sympathetic activity in women at identical work loads may be their relatively smaller skeletal muscle mass in relation to the loads during this test.     

Catecholamines in sow graafian follicles at proestrus and at diestrus

Endogenous dopamine, noradrenaline, and adrenaline were detected in the sow graafian follicular wall and in the follicular fluid. Noradrenaline represented the highest level and adrenaline the lowest. Dopamine and noradrenaline concentrations found in the follicular fluid were lower at early proestrus than at mid-diestrus, whereas adrenaline levels in the fluid did not differ at either stage of the estrous cycle. The sow follicular wall contained less dopamine, noradrenaline and adrenaline at early proestrus than at mid-diestrus. Concomitantly, a decrement of [3H]-dopamine and [3H]-noradrenaline uptake, and of dopamine-beta-hydroxylase activity was detected at early proestrus compared to levels detected at mid-diestrus. The findings in sow graafian follicles show the existence of relationships between hormonal status, dopamine, noradrenaline and adrenaline endogenous levels and uptake, and dopamine-beta-hydroxylase activity. Possible links between estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels during the pig estrous cycle and ovarian catecholamines are discussed, as is a plausible involvement of these neurotransmitters in the contractile activity of the theca layer and the processes of follicular rupture and ovulation.     

Sexual dimorphism for growth in Muscovy ducks and changes in insulin-like growth factor I (IGF-I), growth hormone (GH) and triiodothyronine (T3) plasma levels.

Muscovy ducks display marked sexual dimorphism for body weight. The aim of our study was to analyse the possible relationships between this dimorphism and plasma levels of T3, GH and IGF-I from hatch to 15 weeks of age. We found no significant effect of sex or age on plasma T3 which remained relatively stable about 6 nM x L(-1). Plasma GH levels were highest (14-24 ng x mL(-1)) but highly variable during the first four weeks in females and during the first seven weeks in males. Then, they decreased and remained low (3-4 ng x mL(-1)) until the age of 15 weeks. A trend for higher GH concentrations in males compared to females was observed across the experimental period. The difference was maximum around 6-7 weeks of age. Plasma IGF-I levels rose sharply between 2 and 3 weeks of age and remained high until 6-7 weeks of age for the females and 13 weeks of age for the males then started to decrease. For the whole experimental period, significantly higher IGF-I levels were measured in males. The differences between sexes were significant between 7 and 12 weeks of age and at 14 weeks of age. The differences in circulating GH and IGF-I levels between sexes suggest that the somatotrophic axis is implicated in Muscovy duck sexual dimorphism.     

Identification of a noradrenaline-rich subdivision of the human nucleus accumbens

The nucleus accumbens, situated at the junction between rostral pre-commissural caudate and putamen, is now considered to be critically involved in rewarding and motivational functions mediated by the neurotransmitter dopamine. However, in the human, the precise anatomical boundaries of this nucleus are still undetermined and controversy exists as to the extent to which nucleus accumbens activity is controlled by noradrenaline, a related neurotransmitter now much neglected (in favor of dopamine) by the scientific community. Here we resolve the question of noradrenaline in the human nucleus accumbens and identify, in autopsied brain of normal subjects, a small subdivision of the caudomedial portion of this nucleus that selectively contains strikingly high levels of noradrenaline and thus represents the only area in human brain having equally high levels of both noradrenaline and dopamine. The presence of very high, localized noradrenaline concentrations in the caudomedial nucleus accumbens implies a special biological role for this neurotransmitter in human brain motivational processes.     

The effects of neonatal paternal deprivation on pair bonding, NAcc dopamine receptor mRNA expression and serum corticosterone in mandarin voles

High levels of paternal care are important for the development of social behavior in monogamous rodents. However, the effects of paternal care on the formation of pair bonding and underlying neuroendocrine mechanisms, especially the involvements of dopamine system and corticosterone, are not well understood. We investigated effects of paternal deprivation on pair bonding in mandarin voles (Microtus mandarinus), a socially monogamous rodent. Paternal deprivation was found to inhibit the formation of pair bonding in females according to partner preference tests (PPT). Paternal deprivation also reduced body contact behavior and increased aggression in males and females in PPT. During social interaction tests (SIT), paternal deprivation was found to reduce investigative and aggressive behaviors but increase body contact and self-grooming in females, and reduce staring, aggression, body contact and self-grooming in males when interacting with the opposite sex. Paternal deprivation reduced the expression of dopamine 1-type receptor (D1R) mRNA and dopamine 2-type receptor (D2R) mRNA in the nucleus accumbens of female offspring in later life, but enhanced mRNA expression of these two dopamine receptors in males. After three days of cohabitation the expression of D1R mRNA and D2R mRNA was negatively correlated for voles reared by two parents, but positively correlated in paternally deprived animals. Paternal deprivation reduced serum corticosterone levels in females but had the opposite effect in males. Three days of cohabitation did not alter corticosterone levels of PD females, but reduced it in PC females. Our results provide substantial evidence that paternal deprivation inhibits the formation of pair bonding in female mandarin voles and alters social behavior later in life. These behavioral variations were possibly associated with sex-specific alterations in the expression of two types of dopamine receptors and serum corticosterone levels induced by paternal deprivation.     

Influence of thyroidectomy on brain catecholamines during the postnatal period

The influence of early thyroidectomy (Tx) on changes in dopamine (DA) and noradrenaline (NA) during the postnatal period (30, 45 and 60 days old) was studied in the diencephalon and the rest of the brain of male and female rats. Thyroidectomy interfered with the normal growth of the animals, decreased brain weight and markedly influenced the developmental pattern of both DA and NA in the diencephalon. When compared with control values, the DA concentration, in 45- and 60-day-old Tx male rats, was 29 and 43% lower, respectively, and 21 and 43% lower, respectively, in Tx females. Diencephalic NA levels in Tx rats were also lower than those observed in controls, 15% inferior in 45- and 60-day-old males; 27 and 22% lower, respectively, in females. Thyroidectomy does not significantly alter the level of either amine in the rest of the brain.     

Tryptophan, copper and zinc in hair of healthy subjects. Correlation with differences in hair pigmentation

Tryptophan, copper and zinc levels were determined in the hair of 300 healthy subjects divided by sex, age and hair colour. Sex influences tryptophan content in hair, the levels of this amino acid being higher in males than in females. Tryptophan is also higher in infancy (2-5 years) and in both males and females aging around 80 years and over. Hair colour also influences tryptophan levels, which increase from fair to black hair. Copper levels are similar in hair of both males and females, while those of zinc are higher in women. Age influences the distribution of these two metals in human hair. Copper contents in hair of males are higher at the age 20-40 years. In females, values decrease over the age of 60 years. Instead, zinc levels are higher between 20 and 60 years in males, and between 13 and 19 years in females. As regards hair colour, copper is slightly higher in black hair in males and in fair hair in females, and lower in white hair in both sexes. Zinc values appear to be higher in red and lower in white hair in males. In females they are higher in black hair.     

Endogenous Noradrenaline and Dopamine in Nerve Terminals of the Hippocampus: Differences in Levels and Release Kinetics

The presence and release of endogenous catecholamines in rat and guinea pig hippocampal nerve terminals was studied by fluorimetric HPLC analysis. In isolated nerve terminals (synaptosomes) the levels and breakdown of endogenous catecholamines were determined and the release process was characterized with respect to its kinetics and Ca2+ and ATP dependence. Endogenous noradrenaline and dopamine, but not adrenaline, were detected in isolated hippocampal nerve terminals. For dopamine both the levels and the amounts released were more than 100-fold lower than those for noradrenaline. In suspension, released endogenous catecholamines were rapidly broken down. This could effectively be blocked by monoamine oxidase inhibitors, Ca(2+)-free conditions, and glutathione. The release of both noradrenaline and dopamine was highly Ca2+ and ATP dependent. Marked differences were observed in the kinetics of release between the two catecholamines. Noradrenaline showed an initial burst of release within 10 s after K+ depolarization. The release of noradrenaline was terminated after approximately 3 min of K+ depolarization. In contrast, dopamine release was more gradual, without an initial burst and without clear termination of release within 5 min. It is concluded that both catecholamines are present in nerve terminals in the rat hippocampus and that their release from (isolated) nerve terminals is exocytotic. The characteristics of noradrenaline release show several similarities with those of other classical transmitters, whereas dopamine release characteristics resemble those of neuropeptide release in the hippocampus but not those of dopamine release in other brain areas. It is hypothesized that in the hippocampus dopamine is released from large, dense-cored vesicles, probably colocalized with neuropeptides.