Neurochemical measurements in the brains of mice infected with Trypanosoma brucei brucei (TREU 667)

Trypanosoma brucei brucei (TREU 667) infected mice were used as a model of African trypanosomiasis, a disease in which neuropsychiatric manifestations occur. To study the possible neurochemical basis of these abnormalities, we measured brain acetylcholine receptor numbers, activities of the cholinergic enzymes, choline acetyltransferase (CAT), and acetylcholinesterase (AChE), and regional concentrations of the monoamines, dopamine (DA), serotonin (5-HT), and norepinephrine (NE), and their acid metabolites, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) in mice infected with T. b. brucei. There were no significant changes in CAT or AChE activities or acetylcholine receptor numbers at either 35 or 50 days post-infection (PI). At day 35 PI, the only significant finding was a decrease in 5-HIAA concentration in the brain stem, a change which did not persist to day 50 PI. At day 50 PI there were, however, significant increases in DA concentration in the brain stem and NE concentrations in the hippocampus, cerebellum, brain stem and striatum. To establish a chronic relapsing murine model, mice were treated with diminazene aceturate (Berenil) at day 60 PI and killed 60 days later (120 days PI). In these mice, 5-HT concentrations were significantly increased in the hypothalamus and decreased in the cortex. In addition, 5-HIAA concentrations were increased in the striatum and hypothalamus and HVA concentrations were increased in the striatum and hippocampus. Our data, taken together with that of others, suggests that there are alterations in the monoaminergic, but not in the cholinergic, neuronal system, in African trypanosomiasis. These data may form the basis for the neuropsychiatric abnormalities that are associated with this disease.     

N-acetyl cysteine reverses social isolation rearing induced changes in cortico-striatal monoamines in rats

Schizophrenia is causally associated with early-life environmental stress, implicating oxidative stress in its pathophysiology. N-acetyl cysteine (NAC), a glutathione precursor and antioxidant, is emerging as a useful agent in the adjunctive treatment of schizophrenia and other psychiatric illnesses. However, its actions on brain monoamine metabolism are unknown. Social isolation rearing (SIR) in rats presents with face, predictive and construct validity for schizophrenia. This study evaluated the dose-dependent effects of NAC (50, 150 and 250 mg/kg/day × 14 days) on SIR- vs. socially reared induced changes in cortico-striatal levels of dopamine (DA), serotonin (5-HT) noradrenaline (NA) and their associated metabolites. SIR induced significant deficits in frontal cortical DA and its metabolites, 3,4-dihydroxyphenylacetic acid (Dopac) and homovanillic acid (HVA), reduced 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and reduced levels of the NA metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG). In addition, significant elevations in frontal cortical NA and striatal DA, Dopac, HVA, 5-HT, 5-HIAA, NA and MHPG were also observed in SIR rats. NAC at 150 and 250 mg/kg reversed all cortico-striatal DA, Dopac, HVA, 5-HT, 5-HIAA and striatal NA alterations in SIR animals, with 250 mg/kg of NAC also reversing alterations in cortico-striatal MHPG. In conclusion, SIR profoundly alters cortico-striatal DA, 5-HT and NA pathways that parallel observations in schizophrenia, while these changes are dose-dependently reversed or abrogated by sub-chronic NAC treatment. A modulatory action on cortico-striatal monoamines may explain NACs’ therapeutic use in schizophrenia and possibly other psychiatric disorders, where redox dysfunction or oxidative stress is a causal factor.     

Aging and diurnal rhythms of pineal serotonin, 5-hydroxyindoleacetic acid, norepinephrine, dopamine and serum melatonin in the male rat

Pineal serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE) and dopamine (DA) were measured by high-pressure liquid chromatography with electrochemical detection and serum melatonin was measured by radioimmunoassay in rats aged 3 weeks, 8 weeks and 18 months. They were killed either at mid-light or mid-dark of a 12 h light:12 h dark cycle. Diurnal rhythms were observed for 5-HT and 5-HIAA in all ages studied while those for NE and DA were not observed in the 18-month-old animals. Pineal 5-HT and 5-HIAA were higher in 3-week-old rats at mid-dark, and lower at mid-light than in older animals. The pineal content of NE was lower in the 3-week-old rats at mid-dark and mid-light compared with that in the 8-week-old while the DA content was lower at mid-dark. In addition, pineal 5-HT, 5-HIAA, NE and DA were lower in the 18-month-old than in the 8-week-old animals at mid-dark. At mid-dark serum melatonin levels showed an age-related decrease. This study shows that an age-related decrease of pineal 5-HT, 5-HIAA, NE and DA can only be demonstrated at mid-dark and that the age-related decrease of melatonin may not be due to a decrease in sympathetic activity.     

Intermale competition in sexually mature arctic charr: effects on brain monoamines, endocrine stress responses, sex hormone levels, and behavior

Sexually mature Arctic charr (Salvelinus alpinus) males were allowed to interact in pairs for 4 days in the absence of females. Agonistic behavior was quantified, and at the end of the experiment, plasma levels of glucose, cortisol, testosterone (T), 11-ketotestosterone (11-KT), and 17alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha, 20beta-P) were determined alongside brain concentrations of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA, the major 5-HT metabolite), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC, a major DA metabolite). Plasma cortisol and glucose were significantly elevated in subordinate fish, and the number of aggressive acts received showed positive correlations with plasma levels of glucose on day 1, during the development of the dominance relationship, and of cortisol on day 4, when the dominance relationship was established. In contrast, plasma concentrations of T and 11-KT were significantly higher in dominant than in subordinate males, and there was a similar tendency in plasma concentrations of 17alpha,20beta-P. Further, plasma levels of these gonadal steroids were correlated with the number of aggressive acts performed on day 4, but not with the number of aggressive acts received. The plasma cortisol concentrations did not correlate with either 5-HIAA:5-HT or DOPAC:DA ratios in any of the brain parts analyzed. Plasma glucose levels showed positive correlations with brain 5-HIAA:5-HT ratios. Negative correlations were observed between 5-HIAA:5-HT ratios in the optic tectum and between plasma levels of T, 11-KT, and 17alpha,20beta-P. Telencephalic DOPAC/DA ratios displayed a negative correlation with plasma levels of T, 11-KT, and 17alpha,20beta-P, but only in dominant males.     

Association between Low Contents of Dopamine and Serotonin in the Nucleus Accumbens and High Alcohol Preference

The contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxy-indoleacetic acid (5-HIAA) were determined in the nucleus accumbens (ACB), frontal cortex (FR), anterior striatum (AST), and hippocampus (HIP) of adult male rats from the F₂ generation of P×NP intercrosses. Rats were tested for their alcohol preference and were divided into two groups, depending on their alcohol intake. Rats in the high drinking group ( n = 11) had ethanol intakes >5 g/kg/day, whereas the low drinking group ( n = 15) had values < 1 g/kg/day. The content of DA in the ACB was lower ( p < 0.001) in the high alcohol drinking group (46 ± 2 pmol/mg tissue) than in the low intake rats (61 ± 3 pmol/mg tissue). However, the contents of DOPAC and HVA in the ACB were similar for both groups. There were no differences between the two groups in the contents of DA in the FR or AST. The content of 5-HT in the ACB was lower (p < 0.05) in high alcohol drinking rats (6.3 ± 0.3 pmol/mg tissue) than in the low intake group (7.0 ± 0.2 pmol/mg tissue). The content of 5-HIAA in the ACB of the high intake rats was also lower than the level for the low drinking rats. There were no differences in the contents of 5-HT or 5-HIAA in the FR, HIP, and AST between the two groups. The results confirm a phenotypic association between abnormal DA and 5-HT systems projecting to the ACB and high alcohol drinking behavior in the P line of rats.     

Evidence for a physiological reduction in brain dopamine but not norepinephrine metabolism during the preovulatory phase in normal women

To investigate the role of brain catecholamine (CA) activity in the mechanisms related to physiological ovulatory function, we used high-performance liquid chromatography with electrochemical detector to measure the levels of urinary dopamine (DA), norepinephrine (NE), epinephrine (E), vanillylmandelic acid (VMA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and total 3-methoxy-4-hydroxy-phenylglycol (MHPG) in a group of 12 normal women during both the early follicular and pre-ovulatory phases of the menstrual cycle. The mean (+/- SEM) concentrations of HVA and DOPAC were significantly lower (P less than 0.001) during the pre-ovulatory phase than during the early follicular phase, whereas those of DA, NE, E, VMA and total MHPG were unaltered. A significant negative correlation between urinary HVA and plasma LH (r = -0.70, P less than 0.01) was also found during the pre-ovulatory period, whereas no significant negative correlations were found between urinary HVA and plasma PRL, progesterone and oestradiol. These data show: 1) reduced brain DA activity and 2) unchanged brain NE activity at the time of the midcycle surge in normal women, suggesting a physiological variation of the central DA metabolism in ovulatory function.     

The change with age in biogenic amines and their metabolites in the striatum of the rat

The changes in the content of the biogenic amines and their metabolites in the striatum of the rat during the aging period (3-30 months) have been studied. The maximum levels of dopamine (DA) have been found at 6 months of age and this concentration is maintained until 24 months. Between 24 to 30 months there is a decrease in the concentration of this compound. At that time, there is a slight increase in 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) concentration, the main metabolites of DA, which suggests a slight increase in DA metabolism. The 3-methoxytyramine (3-MT) concentration also increases at this time. The maximum concentration of noradrenaline (NA) was also found at 6 months of age. Tryptophan has the maximum concentration after DA and this is maintained over the life-span of the rat. The concentration of serotonin (5-HT) is high and does not change during this period. However, the concentration of 5-HT, as occurred with DA, decreased between 24 and 30 months. Also the DA/5-HT ratio does not change during the period studied.     

Daidzin and its antidipsotropic analogs inhibit serotonin and dopamine metabolism in isolated mitochondria

Daidzin, a major active principle of an ancient Chinese herbal treatment (Radix puerariae) for alcohol abuse, selectively suppresses ethanol intake in all rodent models tested. It also inhibits mitochondrial aldehyde dehydrogenase (ALDH-2). Studies on ethanol intake suppression and ALDH-2 inhibition by structural analogs of daidzin established a link between these two activities and suggested that daidzin may suppress ethanol intake by inhibiting ALDH-2. ALDH-2 is a principal enzyme involved in serotonin (5-HT) and dopamine (DA) metabolism. Thus, daidzin may act by inhibiting 5-HT and DA metabolism. To evaluate this possibility, we have studied the effect of daidzin and its analogs on 5-HT and DA metabolism in isolated hamster and rat liver mitochondria. Daidzin potently inhibits the formation of 5-hydroxyindole-3-acetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) from their respective amines in isolated mitochondria. Inhibition is concentration-dependent and is accompanied by a concomitant accumulation of 5-hydroxyindole-3-acetaldehyde and 3,4-dihydroxyphenylacetaldehyde. Daidzin analogs that suppress hamster ethanol intake also inhibit 5-HIAA and DOPAC formation. Comparing their effects on mitochondria-catalyzed 5-HIAA or DOPAC formation and hamster ethanol intake reveals a positive correlation—the stronger the inhibition on 5-HIAA or DOPAC formation, the greater the ethanol intake suppression. Daidzin and its active analogs, at concentrations that significantly inhibit 5-HIAA formation, have little or no effect on mitochondria-catalyzed 5-HT depletion. It appears that the antidipsotropic action of daidzin is not mediated by 5-HT (or DA) but rather by its reactive intermediates 5-hydroxyindole-3-acetaldehyde and, presumably, 3,4-dihydroxyphenylacetaldehyde as well, which accumulates in the presence of daidzin.     

Effects of hydrostatic pressure on monoaminergic activity in the brain of a tropical wrasse, Halicoeres trimaculatus: possible implication for controlling tidal-related reproductive activity

Most wrasse species in tropical waters exhibit daily spawning synchrony with a preference for high tide. Fish perceive tidal rhythm cues through sensory organs and activate the brain-pituitary-gonadal endocrine axis for synchronous gonadal maturation, although how the tidal-related spawning cycle is controlled endogenously is not known. The purpose of this study was to examine whether hydrostatic pressure has an impact on brain monoamine levels and reproductive activities in the threespot wrasse Halichoeres trimaculatus. The contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the brain were measured using high-performance liquid chromatography and an electrochemical detection system. Exposing the fish to hydrostatic pressure occurring at a 3-m depth (~30 kPa) resulted in an increase in 5-HIAA/5-HT over 3h and a decrease in DOPAC/DA over 6h. No changes in gonadosomatic index or oocyte diameter were observed between the groups when female fish were reared at 0-m and 3-m depth for 3h. Hydrostatic pressure did not alter pituitary mRNA abundance of follicle stimulating hormone-β or luteinizing hormone-β. However, in vitro culture of ovaries from pressurized fish in the presence of human chorionic gonadotropin resulted in an increase in 17α,20β-dihydroxy-4-pregnen-3-one in the medium. These results suggest that hydrostatic pressure activates oocyte maturation through brain monoaminergic activity in this tropical wrasse species.     

The Effect of Ethanol on the Brain Catecholamine Systems in Female Mice, Rats, and Guinea Pigs

The effect of acute ethanol administration on the concentrations of dopamine (DA), norepinephrine (NE) and their metabolites (3,4-dihydroxyphenylacetic acid [DOPAC], homovanillic acid [HVA], 3,4-dihydroxyphenylglycol [DHPG] and 4-hydroxy-3-methoxyphenylglycol [HMPG]) in brains of female mice, rats, and guinea pigs were investigated. A subhypnotic dose (2 g/kg) or a hypnotic dose (4 g/kg) of ethanol was administered intraperitoneally and the animals were killed 45 min later. In the rat the DA levels were unchanged, while the NE concentrations were decreased after both doses of ethanol. The DA levels did not change in the mouse and guinea pig, while the concentrations of NE showed a minor decrease in the mouse but were unaffected in the guinea pig. After 4 g/kg of ethanol the DOPAC and HVA concentrations were elevated significantly in all three species, and after 2 g/kg the DOPAC levels were increased in the rat and guinea pig brains and the HVA levels in the mouse and guinea pig brains. In the mouse and rat brain the DOPAC + HVA concentrations indicated a dose response relationship: 4 g/kg was significantly more effective than 2 g/kg. The DHPG concentration increased in the rat brain after both 2 and 4 g/kg, while the HMPG concentrations increased significantly only after 2 g/kg. In the mouse and guinea pig the brain DHPG concentrations remained unchanged, while the HMPG concentrations increased after both 2 and 4 g/kg ethanol. These data suggest, that the turnover of both DA and NE was increased 45 min after a subhypnotic as well as after a hypnotic dose of ethanol in all three species studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dopaminergic activity in the brain of a tropical wrasse in response to changes in light and hydrostatic pressure

Many tropical wrasses show a daily pattern of spawning with gamete release typically near daytime high tide. The environmental cues the fish obtains from day-night and tidal cycles to ensure spawning synchrony and how those cues are transduced, however, are not fully understood. To gain insight into these issues, the involvement of monoamines in mediating endogenous day-night and tidal rhythms in the threespot wrasse, Halichoeres trimaculatus, were examined. Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC, a metabolite of DA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA, a metabolite of 5-HT) in the brain of the fish were measured with high-performance liquid chromatography and electrochemical detection. DOPAC and the metabolic rate of DA activity (DOPAC/DA) were found to increase during the day and decrease during the night for fish held under a natural photoperiod. Fish acclimated to a 12:12 light-dark cycle and to constant dark conditions exhibited similar changes, whereas fish acclimated to constant light conditions exhibited little or no change. Intraperitoneal injection of melatonin resulted in a significant reduction in DOPAC/DA. Furthermore, DOPAC/DA was significantly lower in fish held at 3 m compared to 0 m depth, suggesting that hydrostatic pressure influences DA metabolic rate. These results indicate that light and hydrostatic pressure control dopaminergic turnover in the brain of threespot wrasse. Day-night and tidal changes in these two factors therefore may be the main environmental cues the fish uses to synchronize its spawning activity.     

Median eminence dopamine and serotonin neuronal activity. Temporal relationship to preovulatory prolactin and luteinizing hormone surges

Using a high-performance liquid chromatography (HPLC) system coupled with an electrochemical detector, the concentrations of dopamine (DA) and 5-hydroxytryptamine (5-HT) and their major specific metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole-3-acetic acid (5-HIAA), respectively, were measured in the median eminence (ME) throughout the rat estrous cycle. The ME DA content remained fairly constant throughout the estrous cycle except on estrus when 17.00 h values were significantly lower than 10.00 h values (40% decrease, p less than 0.05). The ME 5-HT content determined at 10.00 h was higher on proestrus than on any other day of the cycle. The ME DOPAC concentrations did not differ between 10.00 and 17.00 h on diestrus I, diestrus II or estrus. On the contrary, there was an almost linear decline between 10.00 and 17.00 h on proestrus (36% decrease, p less than 0.05). The ME 5-HIAA content did not differ between 10.00 and 17.00 h on any day of the estrous cycle. Significant changes were recorded for the DOPAC/DA and 5-HIAA/5-HT ratio in the ME on proestrus. There was a progressive decrease, starting from 10.00 h in the DOPAC/DA ratio with minimal values (42% decrease, p less than 0.05) at 16.00 h followed by an increase from 16.00 to 19.00 h. On the other hand, the 5-HIAA/5-HT ratio increased between 10.00 and 17.00 h (97% increase, p less than 0.05) and subsequently declined until 19.00 h (67% decrease vs. 17.00 h, p less than 0.05).2+hese data show that a concomitant     

High concentrations of epinephrine derived from a central source and of 5-hydroxyindole-3-acetic acid in hypophysial portal plasma

This study was designed to determine if active secretion of epinephrine (EPI) and/or 5-hydroxytryptamine (5-HT) from the hypothalamus into the hypophysial portal vasculature takes place, in addition to the well-known secretion of dopamine (DA). Hypophysial portal plasma was collected from urethane-anesthetized male rats by stalk cannulation (Porter method) or by periodic aspiration of portal blood (Worthington and Fink method). Portal and peripheral plasma concentrations of EPI, 5-HT, DA and 5-hydroxyindole-3-acetic acid (5-HIAA) were concurrently measured by high performance liquid chromatography with electrochemical detection. Significantly higher concentrations of EPI were found in hypophysial portal than in peripheral plasma. After adrenalectomy (ADX), peripheral plasma levels of EPI were undetectable, whereas portal plasma EPI levels were only slightly attenuated. Although 5-HT levels in portal and peripheral plasma were not different, 5-HIAA levels were 3-fold higher in portal plasma. DA was 10-15 fold higher in portal plasma. All the above differences were found independent of the collection method. The high level of 5-HIAA in portal plasma was not due to conversion of 5-HT to 5-HIAA by monoamine oxidase in plasma. The results indicate that in addition to DA, another amine (EPI) and an amine metabolite (5-HIAA) have a concentration gradient in portal vs peripheral plasma. Moreover, the presence of EPI in portal plasma after ADX is a strong indication that EPI is primarily derived from a central source, suggesting that the amine may have a direct physiological role in the regulation of anterior pituitary function.     

Effects of idebenone on monoamine metabolites in cerebrospinal fluid of patients with cerebrovascular dementia

Monoamine metabolites and norepinephrine (NE) in the cerebrospinal fluid of patients with cerebrovascular dementia were measured to study the effects of administration of idebenone. Six patients with cerebral infarction and one with cerebral hemorrhage (mean age 65.4 years) were enrolled as subjects. All the patients had mental and intelligence impairment which was evaluated by the Hasegawa's Dementia Rating (DR) Scale. The patients were medicated with a 90 mg/day dose of idebenone for 1 to 2 months, and homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and NE in the cerebrospinal fluid were determined by high-performance liquid chromatography before and after the medication of idebenone. Before the medication, the level of HVA was 21.7 +/- 1.4 ng/ml (mean +/- SE), which was significantly lower (p less than 0.01) as compared with that in control subjects of similar age. The level of 5-HIAA was 18.5 +/- 2.7 ng/ml, and that of MHPG 9.5 +/- 0.7 ng/ml, both of which were lower than those of the controls, though statistically not significant. NE was similar to the control value. After administration of idebenone, HVA measured was 27.1 +/- 3.2 ng/ml, showing a tendency to increase. The levels of 5-HIAA and MHPG were 26.7 +/- 2.3 ng/ml and 10.7 +/- 0.6 ng/ml, respectively, which were significantly (p less than 0.05) higher than the premedication values. The percentages of the change were 12.8 +/- 8.0 for HVA, 58.2 +/- 18.5 for 5-HIAA and 14.2 +/- 5.0 for MHPG. The score of the DR scale was improved by 5 or less after the idebenone medication in most subjects. HVA and 5-HIAA increased markedly in the patients who showed a tendency of improvement of mental impairment as evaluated by the DR scale. The results suggested that idebenone would improve abnormalities in neurotransmitters of patients with cerebrovascular dementia, especially promoting serotonin turnover.     

Aromatic L-amino acid decarboxylase activity in the rat median eminence, neurointermediate lobe and anterior lobe of the pituitary. Physiological and pharmacological implications for pituitary regulation

Recent evidence demonstrating a direct effect of 5-hydroxytryptamine (5-HT) upon anterior pituitary (AP) hormone secretion has made the question of determining the location of possible sites that could supply 5-HT to the AP an important one. It has been assumed, based on indirect evidence, that aromatic L-amino acid decarboxylase (L-AAD), the enzyme responsible for the conversion of L-5-hydroxytryptophan (5-HTP) to 5-HT as well as L-3,4-dihydroxyphenylalanine (L-dopa) to dopamine (DA), is ubiquitously distributed in most tissues of the body including the AP. The present study examined the ability of the AP and two neural areas anatomically connected to the AP, the neurointermediate lobe (NIL) of the pituitary and the median eminence (ME), to decarboxylate 5-HTP to 5-HT or L-dopa to DA following either the in vitro incubation of the various tissues with 5-HTP or L-dopa or the in vivo administration of 5-HTP to rats treated previously with saline or a peripheral decarboxylase inhibitor, MK 486. The in vivo effects of 5-HTP, alone, or following MK 486 pretreatment were also examined on 5-HT synthesis and metabolism in AP tissues which were transplanted 5 days previously under the renal capsule and were, thus, isolated from central influences that might be regulating 5-HT and 5-hydroxyindole-3-acetic acid (5-HIAA) concentrations in the animal's own AP. In addition, the direct radioisotopic measurement of L-AAD activity in the ME, NIL, and AP was also analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of acute ether stress on monoamine metabolism in median eminence and discrete hypothalamic nuclei of the rat brain and on anterior pituitary hormone secretion

This study was designed to correlate the endocrine responses elicited by acute ether stress with the changes in metabolism of several monoamines in discrete nuclei of the rat brain. Concentrations of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) and also of the specific metabolites of NE, DA, and 5-HT, 3-methoxy-4-hydroxyphenylethylene glycol, 3,4-dihydroxyphenylacetic acid, and 5-hydroxyindole-3-acetic acid, respectively, were concurrently measured in microdissected nuclei using high-performance liquid chromatography with electrochemical detection. The ratio of the metabolites to their respective amines was used as an estimate of the metabolism of NE, DA, and 5-HT. Acute exposure to ether vapors induced, within 5-15 min, large increments in plasma levels of adrenocorticotropic hormone (ACTH), beta-endorphin, and prolactin (PRL), and decrements in the levels of plasma growth hormone (GH). Significant increases in NE metabolism were observed in the rostral (ANr) and caudal (ANc) divisions of the arcuate nucleus, as well as in the paraventricular (PVN) and dorsomedial nuclei, 15 min after ether stress. A significant decrease in 5-HT metabolism was observed in the PVN, supraoptic nucleus, and ANc, whereas significant increases in 5-HT metabolism were detected in the suprachiasmatic nucleus and ANr. DA metabolism selectively increased in the ANr. The present results indicate that the acute changes in ACTH, beta-endorphin, PRL, and GH release induced by ether exposure are temporally correlated with increases in NE metabolism in many hypothalamic nuclei; a selective increase in DA metabolism restricted to the ANr, and differential effects on 5-HT metabolism, probably reflecting selective activation or inhibition of different populations of 5-HT neurons.     

Daily variation in the content of indoleamines, catecholamines and related compounds in the pineal gland of Syrian hamsters kept under long and short photoperiods

Abstract: This study examined the diurnal changes in the content of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), N-acetylserotonin (NAS), melatonin, 5-methoxytryptophol (5-ML), noradrenaline (NA), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC) in the pineal gland of Syrian hamsters kept under long (14L: 10D) and short (10L: 14D) photoperiods. The nocturnal increase in NAS and melatonin levels was dependent upon the prevailing photoperiod, with a prolonged duration when the night lengthened. In both photoperiods, NAS and melatonin contents increased several hours after the onset of darkness, and, in animals kept in short photoperiod, the levels of both compounds began to decrease before light onset. On the contrary, decreases were noted in 5-HT, 5-HIAA, and 5-ML contents during the night, which was directly proportional to the dark phase. 5-HTP levels did not show a rhythmic variation. Correlations between the mean values of 5-HT-related compounds showing daily rhythms were very high when group means were compared, but they decreased when values from individual animals were considered. In addition, when correlations were calculated on per-animal basis during the night phase, a weak negative correlation was found for 5-HT vs NAS and 5-HT vs melatonin, although the correlation of 5-HT with positively 5-HT-correlated compounds (5-HIAA and 5-ML) continued to be high. These results indicate that the nocturnal increase in the N-acetyl transferase activity is the major factor generating the rhythm of pineal 5-HT content, but that other photoperiod-dependent mechanisms (i.e., 5-HT synthesis or release) seem to be also implicated. On the other hand, this study shows that NA content in the Syrian hamster pineal gland does not exhibit daily variations, although marked nocturnal increases in the levels of DA and DOPAC were evident. These results suggest the existence of parallel daily alterations in pineal catecholamine synthesis and release, and suggest a role for DA in the pineal activation at night.     

T3对体外培养的大鼠胚胎大脑神经细胞神经递质代谢的影响

本文采用无血清培养液(SFM),加入生理浓度的 T_3,观察 T_3对15—18天大鼠胚胎大脑神经细胞神经递质代谢的影响。发现 T_3能明显促进体外培养的胎鼠大脑神经细胞合成,分泌单胺类神经递质,促进神经细胞发育成熟。     

Mechanisms of 5-hydroxy-L-tryptophan-induced adrenocorticotropin release: a major role for central noradrenergic drive

The serotonin (5-hydroxytryptamine, 5-HT) precursor 5-hydroxy-L-tryptophan (5-HTP) and 5-HT antagonists, respectively, are able to stimulate and block pituitary adrenocorticotropin (ACTH) release. However, our previous data do not support a role of central serotoninergic systems in the neural control of ACTH release. We thus examined the hypothesis that 5-HTP given either alone or with uptake-blocking drugs such as fluoxetine caused stimulation of ACTH through activation of central noradrenergic neuronal activity (NNA). The hypothesis was tested in normal adult male rats by correlating medial basal hypothalamic NNA and serotoninergic neuronal activity (SNA) with serum ACTH following administration of 5-HTP (20 and 100 mg/kg, i.p.) in the presence or absence of fluoxetine (10 mg/kg, i.p.) or cyproheptadine (10 mg/kg, i.p.). The alpha 2-adrenergic agonist clonidine (150 micrograms/kg, i.p.) was used to inhibit central NNA and to examine the role of alpha 2-adrenoceptors in the actions of serotoninergic drugs. Computerized mass spectrometry was employed to specifically and precisely assay hypothalamic norepinephrine (NE), 3,4-dihydroxyphenylethyleneglycol (DHPG), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) to obtain indices of hypothalamic NNA (DHPG/NE) and SNA (5-HIAA/5-HT). The administration of fluoxetine/5-HTP stimulated (p less than 0.01) both hypothalamic NNA and ACTH release.(ABSTRACT TRUNCATED AT 250 WORDS)     

Food deprivation and refeeding effects on pineal indoles metabolism and melatonin synthesis in the rainbow trout Oncorhynchus mykiss

The effects of food deprivation and refeeding on daily rhythms of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and melatonin contents, as well as on arylalkylamine N-acetyltransferase (AANAT) activity were evaluated in the pineal organ of rainbow trout. In addition, changes in circulating melatonin and cortisol levels were tested at one single point at day and night. Immature rainbow trout were distributed in 3 experimental groups: fish fed, fish fasted (7 days), and fish fasted for 7 days and refed for 5 days. All fish were sampled from each treatment group at different times of the day-night cycle. Pineal melatonin levels and AANAT activity showed daily variations in either fed, fasted and refed trout, displaying highest values at night. Fasted trout showed reduced melatonin content throughout the 24-h cycle, which was associated with decreased AANAT activity. Rhythms of pineal 5-HT and 5-HIAA levels were evident in all groups and were negatively correlated to melatonin in fed fish groups, but not in fasted fish. A higher content of 5-HT and 5-HIAA was observed in fasted fish during the night with no apparent changes during daytime for 5-HT and increased 5-HIAA levels. Furthermore, decreased circulating levels of melatonin were observed at midday, but not at night, in food deprived trout. Refeeding for 5 days generally counteracted the effects of food deprivation. Cortisol levels in plasma were reduced after food deprivation and remained low in refed fish. The results show that food deprivation impairs daily rhythms of melatonin content in trout pineal organ by affecting the activity of melatonin synthesizing enzymes rather than by a deficiency in substrate availability.