Effect of Melatonin Treatment on 24-hour Variations in Hypothalamic Serotonin and Dopamine Turnover During the Preclinical Phase of Freund's Adjuvant Arthritis in Rats

The effect of melatonin treatment on time-of-day variations in hypothalamic serotonin (5-HT) and dopamine (DA) turnover was studied in rats treated with Freund's complete adjuvant (FCA). Animals received s.c. injections of 30 æg of melatonin or vehicle 1 h before lights off for 11 days. On day 10 of treatment, FCA or its vehicle was s.c. injected, and 2 days later, the rats were killed at 6 different time intervals throughout a 24-hour cycle. Hypothalamic 5-HT, 5-hydroxyindole-3-acetic acid (5-HIAA), DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured by HPLC. 5-HT and DA turnover were estimated from the 5-HIAA/5-HT and DOPAC/DA ratios, respectively. In the anterior hypothalamus, time-of-day variation in 5-HT turnover was suppressed by FCA, an effect counteracted by melatonin treatment. Melatonin also prevented FCA effect on medial hypothalamic 5-HT turnover, while in the posterior hypothalamus, similar daily variations of 5-HT turnover were found in all experimental groups. As far as DA turnover, FCA or melatonin administration suppressed its daily variations in the anterior hypothalamus. Time-of-day variations in medial hypothalamic DA turnover were similar in all groups while only rats treated with melatonin and FCA or its vehicle exhibited significant daily changes of DA turnover in the posterior hypothalamus. Results indicate that melatonin treatment affects partly the 24-hour pattern of variation of hypothalamic 5-HT and DA turnover at an early phase of FCA arthritis in rats.     

Effect of barbitone sodium and thiopental sodium on brain dopamine, noradrenaline, serotonin and 5-hydroxyindoleacetic acid content in Arvicanthis niloticus

The quantitative estimation of total dopamine (DA), noradrenaline (NE), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content in the whole brain tissue of normal Nile grass rat, Arvicanthis niloticus, gives and average of 631 +/- 12 ng DA/g, 366 +/- 12 ng NE/g, 617 +/- 15 ng 5-HT/g and 431 +/- 10 ng 5-HIAA/g fresh brain tissue. The effect of barbitone sodium and thiopental sodium on the total DA, NE, 5-HT and 5-HIAA content in the brain tissue of the Nile grass rat, Arvicanthis niloticus, was studied. The total DA, NE, 5-HT and 5-HIAA contents were determined 5 hr after i.p. injection of different doses of barbitone sodium (20, 40 and 80 mg/ml/100 g body wt) and thiopental sodium (5, 10 and 20 mg/ml/100 g body wt). The effect of different time intervals (1, 10, 30 min, 1, 2.5, 5, 8, 16, 24 and 48 hr) on the total brain DA, NE, 5-HT and 5-HIAA content was investigated after i.p. injection of 40 mg of barbitone sodium and 10 mg of thiopental sodium/ml/100 g body wt. Both barbitone sodium and thiopental sodium caused an increase in DA, NE and 5-HT content and a decrease in 5-HIAA content in the brain tissue of Arvicanthis niloticus. The increase in the whole brain contents of DA, NE and 5-HT after the administration of barbitone sodium and thiopental sodium may be due either to inhibition of transmitter release by an action at the monoamine nerve terminal or to effects causing a decrease in nerve impulse flow. On the other hand, the decrease in 5-HIAA may be due to the decrease in the turnover of 5-HT.     

Monoamine Synthesis and Concentration in Neonatal Rat Brain During Hypercapnia and Recovery

One-day-old rats were exposed to a gas mixture of 15% CO2-21% O2-64% N2 for a 30-min period. Monoamine synthesis in whole brain was measured during, and at various intervals after, hypercapnia by estimating the accumulation of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) after inhibition of aromatic L-amino-acid decarboxylase with NSD 1015. Endogenous concentrations of tyrosine, dopamine (DA), noradrenaline (NA), tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured at the same intervals. Exposure to CO2 induced an increased synthesis of catecholamines and 5-HT. Further, an increase in DA concentration was seen during hypercapnia, while NA and 5-HT were unchanged. After the CO2 exposure the increased in vivo synthesis rates of catecholamines and 5-HT were rapidly normalized, as was the endogenous DA concentration. A slight increase in 5-HT and 5-HIAA concentrations was seen immediately after CO2 exposure. These results indicate that in neonatal animals, hypercapnia induces changes in central monoamine neurons, primarily an increased synthesis. These alterations may be relevant to some physiological changes seen during CO2 exposure, such as the alteration in central respiratory performance.     

Neurochemical asymmetries in the albino rat's cortex, striatum, and nucleus accumbens

The concentrations of dopamine (DA), norepinephrine (NE), serotonin (5-HT), dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the right and left cortex, striatum, and nucleus accumbens of adult Purdue-Wistar rats. There was more DA in the right cortex and accumbens and a greater concentration of NE in the left striatum. There is more 5-HT in the left striatum and right accumbens, more 5-HIAA in the left cortex, as well as a greater 5-HT turnover in the left accumbens. These results are considered in the light of previous findings concerning the relationship of neurochemical asymmetries and behavioral lateralization.     

Neurotensin perfused in hypothalamus of sated or fasted rat: HPLC analysis of release of DA, NE and 5-HT and their metabolites

This investigation was undertaken in the unrestrained rat to determine the localized effect of neurotensin (NT) on the profile of release and turnover of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) within the hypothalamus. Following stereotaxic implantation of a permanent guide tube, artificial CSF was perfused in the hypothalamus of the freely moving animal by means of push-pull cannulae at a rate of 20 μl/min and for an interval of 5.0 min. After three 5.0 min control samples were collected, NT in a concentration of 0.1 μg/μl was perfused followed by additional CSF controls. Assay by HPLC-EC of each perfusate showed that when the rat was sated, NT evoked a significant increase in the release of DA and DOPAC from the hypothalamus as well as augmented NE turnover, as reflected by a significant efflux in MHPG. However, when the rat was fasted for 22 hr, the perfusion of NT reduced DA and DOPAC concentrations in the diencephalic perfusate significantly as well as levels of both MHPG and VMA. Under both sated and fasted conditions, NT failed to produce notable changes in the release of 5-HT or its metabolism to 5-HIAA. These findings thus reveal a functional interaction between NT and both of the catecholamine neurotransmitters within hypothalamic neurons, which is clearly dependent upon the nutritional status of the animal.     

Age-related changes in 24-hour rhythms of norepinephrine content and serotonin turnover in rat pineal gland: effect of melatonin treatment

The 24-hour rhythms of pineal norepinephrine (NE) content and serotonin (5-HT) turnover [estimated from the ratio of 5-hydroxyindoleacetic acid (5-HIAA) to 5-HT] were studied in young (2 months) and aged (18-20 months) Wistar rats killed at 6 different time points throughout a 24-hour cycle. In the first study, significant changes dependent on the time of day were identified, with acrophases in the first half of the activity span for both parameters. Old rats showed significantly smaller mesor and amplitude of the 24-hour rhythm of pineal NE content. They also showed decreased amplitude of the pineal 5-HT turnover rhythm, in the absence of changes in mesor. In old rats, pineal 5-HT and 5-HIAA concentrations were 41-47% of those found in young rats. In a second study, young and old rats received daily intraperitoneal injections of melatonin (30 microg) or vehicle for 11 days at 19.00 h (i.e. 11 h after light on). Analyzed as a main factor in a factorial analysis of variance, both pineal NE content and 5-HT turnover decreased in old rats while pineal 5-HT turnover increased after melatonin treatment. Melatonin treatment augmented the amplitude of the 24-hour rhythm of pineal NE content by 120 and 52% in young and old rats, respectively. The amplitude of the 24-hour rhythm of pineal 5-HT turnover almost doubled after melatonin treatment in young rats and did not change in old rats. Melatonin injection did not modify the rhythm's acrophase. The results indicate that old rats had lower amplitude and lower mesor values of 24-hour variations in pineal NE content and 5-HT turnover. Melatonin treatment only partly restored pineal NE content and was devoid of activity on pineal 5-HT turnover and 5-HT and 5-HIAA concentration in old rats. Impairment of pineal melatonin synthesizing capacity and intrapineal responses to melatonin may underlie pineal aging in rats.     

Changes in catecholamine levels and turnover rates in hypothalamic,vocal control,and auditory nuclei in male zebra finches during development

The catecholamines norepinephrine (NE) and dopamine (DA) have been implicated in the sexual differentiation of brain and behavior and in species-specific learning in several species. To determine if these neurotransmitters might be involved in sexual differentiation of the vocal control system and song learning in male zebra finches, NE and DA levels and turnover rates were quantified in 10 behaviorally relevant brain nuclei [6 vocal control (VCN), 2 auditory (AN), and 2 hypothalamic (HN)] at four critical points during sexual differentiation of the VCN and the period of song learning, 25, 35, 55, and 90 days of age. Some birds were pretreated with α-methyl-para-tyrosine (αMPT) to allow estimation of NE and DA turnover rates. NE and DA levels in microdissected nuclei were quantified using high-performance liquid chromatography with electrochemical detection. αMPT treatment suppressed catecholamine synthesis just as effectively in juveniles as it does in adults and proved an effective method for estimating NE and DA turnover rates. Patterns of NE and DA function in most VCN and AN over development were quite different from those in HN in which NE and DA function changed gradually and showed no striking peaks. NE turnover rates changed significantly over development in all six VCN [nucleus interfacialis (Nlf), high vocal center (HVC), nucleus robustus of the archistriatum (RA), dorsomedial portion of the intercollicular nucleus (DM), Area X of the parolfactory lobe, and lateral portion of the magnocellular nucleus of the anterior neostriatum (IMAN)]; one AN [nucleus mesencephalicus lateralis pars dorsalis (MLd)], and one HN [preopticus anterior (POA)]. NE levels changed significantly in two VCN (Nlf and Area X). In Nlf, RA, Area X, IMAN, and MLd, NE levels and/or turnover rates showed a striking peak at day 25, which was not seen in HN. Both DA levels and turnover rates changed profoundly over development in 5 of 6 VCN (Nlf, RA, DM, Area X, and IMAN) and both AN (MLd and Field L). These nuclei showed striking peaks in DA levels and turnover rates, primarily on day 35 and/or 55, which then declined profoundly by day 90. This contrasted with the minimal change in DA turnover rates seen in one HN (POA) and the sixth VCN, HVC. In several VCN and AN, NE and DA levels and turnover rates during development reached levels never seen in adult males. Previous research has shown that catecholamine function is heightened in VCN during development compared to surrounding tissues. Our data demonstrate that NE and DA function during development shows pronounced peaks in most VCN not seen in HN. This is interesting because both VCN and HN are hormone sensitive, and both show hormone-modulated NE and DA function in adult males. The timing of these peaks suggests that increased catecholaminergic function may be involved in sexual differentiation of the VCN and song learning in finches. © 1998 John Wiley & Sons, Inc. J Neurobiol 34: 329–346, 1998     

Effects of chlorpromazine on hypothalamic aminergic neurons and stress responses in moderate cold

Guinea-pigs were treated with chlorpromazine or 0.9% NaCl and exposed to +4 degrees C or +23 degrees C for 2 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum and urinary catecholamines, muscle and liver glycogen and blood glucose were also measured. Chlorpromazine caused deep hypothermia at this moderately cold temperature and slight hypothermia at room temperature. Cold increased the activity of noradrenergic and serotonergic neurons, as indicated by the increase in hypothalamic MHPG and 5-HIAA and also the MHPG:NA and 5-HIAA:5-HT ratios. A tendency towards drug-induced inhibition of hypothalamic serotonergic neurons was seen, although this was not significant. A drug-induced inhibition of noradrenergic neurons could not be ruled out. Increased drug-induced turnover of DA was observed in the cold, and a tendency in the same direction was seen at room temperature. Excretion of DA into the urine was induced by chlorpromazine. The hypothermic guinea-pigs had low serum catecholamines, indicating diminished sympathetic activity, but high urinary catechols, a sign of cold stress.     

Nicotine-Induced Changes in Neurotransmitter Levels in Brain Areas Associated with Cognitive Function

Nicotine, one of the most widespread drugs of abuse, has long been shown to impact areas of the brain involved in addiction and reward. Recent research, however, has begun to explore the positive effects that nicotine may have on learning and memory. The mechanisms by which nicotine interacts with areas of cognitive function are relatively unknown. Therefore, this paper is part of an ongoing study to evaluate regional effects of nicotine enhancement of cognitive function. Nicotine-induced changes in the levels of three neurotransmitters, dopamine (DA), serotonin (5-HT), norepinepherine (NE), their metabolites, homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), and their precursor, L-DOPA, were evaluated in the ventral and dorsal hippocampus (VH and DH), prefrontal and medial temporal cortex (PFC and MTC), and the ventral tegmental area (VTA) using in vivo microdialysis in awake, freely moving, male Sprague-Dawley rats. The animals were treated with acute nicotine (0.5 mg/kg, s.c.) halfway through the 300-min experimental period. The reuptake blockers, desipramine (100 microM) and fluoxetine (30 microM), were given to increase the levels of NE and 5-HT so that they could be detected. Overall, a nicotine-induced DA increase was found in some areas, and this increase was potentiated by desipramine and fluoxetine. The two DA metabolites, HVA and DOPAC, increased in all the areas throughout the experiments, both with and without the inhibitors, indicating a rapid metabolism of the released DA. The increase in these metabolites was greater than the increase in DA. 5-HT was increased in the DH, MTC, and VTA in the presence of fluoxetine; its metabolite, 5-HIAA, was increased in the presence and absence of fluoxetine. Except in the VTA, NE levels increased to a similar extent with desipramine and fluoxetine. Overall, nicotine appeared to increase the release and turnover of these three neurotransmitters, which was indicated by significant increases in their metabolites. Furthermore, DA, and especially HVA and DOPAC, increased for the 150 min following nicotine administration; 5-HT and NE changes were shorter in duration. As gas chromatography experiments showed that nicotine levels in the brain decreased by 75% after 150 min, this may indicate that DA is more susceptible to lower levels of nicotine than 5-HT or NE. In conclusion, acute nicotine administration caused alterations in the levels of DA, 5-HT, and NE, and in the metabolism of DA and 5-HT, in brain areas that are involved in cognitive processes.     

Age-related changes in secretion of luteinizing hormone and metabolism of hypothalamic amines in bull calves prior to puberty

Effects of age and castration on secretion of luteinizing hormone (LH) and metabolism of hypothalamic monoamines were determined in Holstein bulls. Calves were assigned to be intact or castrated and killed at 8, 12, or 24 wk of age. Animals were castrated and bled every 10 min for 6 h at 96 and 24 h prior to slaughter, respectively. The stalk median eminence (SME), medial basal (MBH), and anterior-preoptic (AHA-POA) hypothalamic regions were obtained at slaughter and assayed for norepinephrine (NE), dopamine (DA), dihydroxy-phenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindole-acetic acid (5-HIAA) using high performance liquid chromatography with electrochemical detection (HPLC-EC). Concentrations of LH and testosterone in plasma were determined by radioimmunoassay (RIA). In intact calves, LH pulse frequency (pulses/6 h) increased between 8 and 12 wk (1.4 vs. 3.4) and then declined (1.6 at 24 wk of age). Frequency of LH discharges did not change during the first 72 h post-castration in calves 8 (1.4 vs 1.0) and 12 (3.4 vs. 3.8) wk of age, but increased in 24-wk-old calves during this time (1.6 vs. 6.4). The amplitude of LH pulses increased with age (p less than 0.05) and after castration (p less than 0.05). There were marked regional differences in concentrations of monoamines. However, effects of age and castration on concentrations of monoamines were observed only within the SME where DA, DOPAC and NE increased significantly with age. Plasma concentrations of testosterone were correlated with concentrations of NE and DOPAC within the SME. Changes in 5-HT with age were biphasic; at each age, 5-HT increased after castration. From these data, it is concluded that 1) different mechanisms regulate LH pulse frequency and amplitude in calves as early as 8 wk of age, and 2) differences in hypothalamic metabolism of monoamines may be related to maturational changes in secretion of LH in bull calves.     

Turnover of Dopamine and Serotonin and Their Metabolites in the Striatum of Aged Rats

Turnover of dopamine (DA), serotonin [5-hydroxytryptamine (5-HT)], and their metabolites has been measured in adult and aged rats. Turnover rates of 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxy-3-indoleacetic acid (5-HIAA) have been assayed from the disappearance rates after blocking by pargyline inhibition of monoamine oxidase (MAO) and from the accumulation rates by probenecid inhibition of the probenecid-sensitive transport system. DA and 5-HT turnover rates have been measured as accumulation rates of 3,4-dihydroxyphenylalanine and 5-hydroxytryptophan, respectively, after central decarboxylase inhibition by 3-hydroxybenzylhydrazine (NSD-1015) and as accumulation rates of DA and 5-HT after pargyline inhibition of MAO. The DA turnover rate after NSD-1015 was 23.9% lower in aged rats than in adults, whereas after pargyline there was no significant difference between the two age groups. The HVA fractional rate constant and turnover after pargyline were lower in aged rats than in adults, and HVA turnover after probenecid was higher in aged rats than in adults. The DOPAC-HVA pathway seems to be reinforced at the expense of DOPAC conjugation. In aged and adult rats whose 5-HT steady-state levels were not statistically different, the 5-HT turnover rate after pargyline and NSD-1015 treatment was lower in aged rats than in adults. An increase of 5-HIAA levels after pargyline and probenecid treatment in aged rats could be due to the handling stress.     

Analysis of γ-Aminobutyric AcidA Receptor Subunits in the Mouse Cochlea by Means of the Polymerase Chain Reaction

Abstract: Unlike 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces consistent decreases in levels of striatal dopamine (DA) with considerably smaller and more variable effects on mouse brain levels of serotonin (5-HT) and norepinephrine (NE), a novel amine-substituted MPTP analogue, 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH₂-MPTP), administered in a standard mouse dosing paradigm for MPTP (20 mg/kg X 4) did not affect striatal DA but led to marked reductions (60–70%) in levels of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and NE measured in frontal cortex and hippocampus 1 week after treatment. Another 2'-substituted MPTP analogue, 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine, affected cortical and hippocampal 5-HT, 5-HIAA, and NE only minimally, while markedly reducing the DA content in striatum (90%), thus indicating that the substituent (-NH₂ versus -CH₃) at the 2'position is important for the differential effects of these MPTP analogues. In a replication study with a 3-week end point, hippocampal and cortical 5-HT, 5-HIAA, and NE levels remained depressed with no indication of recovery. These results suggest that 2'-NH₂-MPTP may be a novel, regionally selective neurotoxin for serotonergic and norad-renergic nerve terminals.     

Neuropeptide Y perfused in the preoptic area of rats shifts extracellular efflux of dopamine,norepinephrine and serotonin during hypothermia and feeding

This study examined the localized action of neuropeptide Y (NPY) on monoamine transmitter activity in the hypothalamus of the unrestrained rat as this peptide induced hypothermia, spontaneous feeding or both responses simultaneously. A guide tube was implanted in the anterior hypothalamic pre-optic area (AH/POA) of Sprague-Dawley rats. Then either control CSF vehicle or NPY in a dose of either 100 ng/μl or 250 ng/μl was perfused by push-pull cannulae in this structure in the fully sated, normothermic rat. Successive perfusions were carried out at a rate of 20 μl/min for 6.0 min with an interval of 6.0 min elapsing between each. Samples of perfusate were assayed by HPLC for their levels of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their respective metabolites. Whereas control CSF was without effect on body temperature (T_b) or feeding, repeated perfusions of NPY over 3.0 hr caused dose—dependent eating from 4 to 39 g of food, hypothermia of 0.9 to 2.3°C or both responses concurrently. As the rats consumed 11–39 g of food, the efflux of NE, MHPG, DOPAC and 5-HT was enhanced significantly, whereas during the fall in T_b the efflux of NE, DOPAC and 5-HIAA from the AH/POA increased. When the T_b of the rat declined simultaneously with eating behavior, the levels in perfusate of DOPAC and HVA increased significantly while MHPG declined. During perfusion of the AH/POA with NPY the turnover of NE declined while DA and 5-HT turnover increased during hypothermia alone or when accompanied by feeding. These results demonstrate that the sustained elevation in NPY within the AH/POA causes a selective alteration in the activity of the neurotransmitters implicated in thermoregulation, satiety and hunger. These findings suggest that both DA and NE comprise intermediary factors facilitating the action of NPY on neurons involved in thermoregulatory and ingestive processes. The local activity of NPY on hypothalamic neurons apparently shifts the functional balance of serotonergic and catecholaminergic neurons now thought to play a primary role in the control of energy metabolism and caloric intake.     

Two-way avoidance and acute shock stress induced alterations of regional noradrenergic, dopaminergic and serotonergic activity in Roman high- and low-avoidance rats

Various brain regions of male RHA/Verh and RLA/Verh rats were dissected out and deep-frozen immediately after 30 min in a shuttle box involving a) no shock (control), b) 40 inescapable shocks or c) 40 avoidable shocks. The RHA/Verh rats used in the "c" category exhibited about 80-85% learned avoidance. 5-HT, 5-HIAA, NA, MHPG-SO4, DA, DOPAC and HVA levels were subsequently measured in selected regions. NA levels were considerably reduced in the hypothalamus and pons/medulla of both selected lines of rats after acute shock stress, supporting the results of numerous studies which have indicated that NA turnover is nonspecifically increased by all types of stress, at least in those regions. An increase in cortical MHPG-SO4 and a reduction in hypothalamic 5-HT seen after avoidance learning also occurred after shock stress in RHA/Verh rats. Whereas RLA/Verh rats showed an increased metabolism of 5-HT in the hypothalamus and pons/medulla after shock stress, RHA/Verh rats showed the opposite response in the hypothalamus after the same treatment. A reduction in 5-HT metabolism was also evident in RHA/Verh rats, after avoidance learning, in the cortex, hippocampus and hypothalamus. These results indicated, pending further studies regarding, for example, possible genetic differences in tryptophan uptake and utilization, that 5-HT probably plays at least a modulatory role in the reaction to stress, and in avoidance behavior. That role may be either active or passive, depending upon the emotional status of the subjects. In regard to the DA responses measured in striatum and hypothalamus of the two rat lines, some divergent inter-treatment tendencies, as well as some similarities, were seen in DA metabolism in both regions, but almost none of the differences were significant.     

Effects of acute 17alpha-methyltestosterone,acute 17beta-estradiol,and chronic 17alpha-methyltestosterone on dopamine,norepinephrine and serotonin levels in the pituitary,hypothalamus and telencephalon of rainbow trout (Oncorhynchus mykiss)

This study investigated: (a) the effects of acute 17alpha-methyltestosterone (MT) or 17beta-estradiol (E(2)) administration on norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3,4, dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) contents in the hypothalamus, telencephalon and pituitary of previtellogenic female rainbow trout Oncorhynchus mykiss, and (b) the effects of chronic MT administration on the levels of these neurotransmitters in these brain regions in immature male rainbow trout. The acute administration of MT induced a significant decrease in pituitary levels of DOPAC as well as in the DOPAC/DA ratio. On the other hand, the acute administration of E(2) induced an increase in pituitary 5-HT levels as well as a decrease in the 5-HIAA/5-HT ratio. In a second experiment, 20 mg MT per kilogram body weight was implanted for 10, 20 or 40 days into sexually immature male rainbow trout. Implanted rainbow trout showed increased testosterone and decreased E(2) levels. In the pituitary, MT induced long-term decreases in NE, DA, DOPAC and 5-HT levels, as well as in the DOPAC/DA ratio. Hypothalamic and telencephalic DA, NE and 5-HT levels were not affected by MT implantation. However, 5-HIAA levels and the 5-HIAA/5-HT ratio were reduced by MT implantation in both brain regions. These results show that chronic treatment with MT exerts both long-term and region-specific effects on NE, DA, and 5-HT contents and metabolism, and thus that this androgen could inhibit pituitary catecholamine and 5-HT synthesis. A possible role for testosterone in the control of pituitary dopaminergic activity and gonadotropin II release is also discussed.     

Asymmetric metabolism of hypothalamic catecholamines alternates with side of ovulation in a lizard (Anolis carolinensis).

We determined levels of monoamines and their metabolites in 2 hypothalami dissected from the right and left hemibrains of 15 females during the right-left alternating ovulatory cycle of Anolis carolinensis. Tissue contents of the following were measured using HPLC and electrochemical (coulometric) detection: dopamine (DA) and its metabolite 2,4-dihydroxyphenylacetic acid (DOPAC), norepinephrine (NE) and its metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG), and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA). An asymmetry ratio (AR) was determined by subtracting hypothalamic content (pM/mg) on the larger ovary (LO) side from that on the smaller ovary (SO) side, divided by the sum of the 2 sides (AR = SO - LO/SO+LO). The Ar of MHPG and DHPG both decreased as the largest follicle in the LO grew during the cycle, from greater than 0 (content higher on the SO side) at the beginning of the cycle to less than 0 (content higher on the LO side). The average content of MHPG in the 2 sides significantly increased during the cycle. There were no significant asymmetric changes in hypothalamic DA or DOPAC. The average content of DA increased during the cycle, whereas the content of DOPAC, as well as DOPAC/DA, did not change. The average content of 5-HT increased, and the average metabolite ratio of 5-HIAA/5-HT decreased during the cycle without significant asymmetries. The metabolite ratios of NE and DA, but not 5-HT, were asymmetric on the same side in a given female.(ABSTRACT TRUNCATED AT 250 WORDS)     

3,4-Dihydroxyphenylethylamine and 5-Hydroxytryptamine Metabolism in the Rat: Acidic Metabolites in Cisternal Cerebrospinal Fluid Before and After Giving Probenecid

3,4-Dihydroxyphenylethylamine (DA, dopamine) and 5-hydroxytryptamine (5-HT) turnover values were determined in freely moving male rats by measuring the rates of accumulation of the acidic metabolites of the above transmitters, i.e., 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in cisternal cerebrospinal fluid (CSF) samples after probenecid (200 mg/kg i.p.) administration. Determinations on samples before and after acid hydrolysis showed that the latter procedure was necessary for DA turnover determination. Thus whereas total (DOPAC + HVA) increased linearly with time after probenecid, free (DOPAC + HVA) did not. This was because the percentage of DOPAC + HVA in conjugated form increased with time. Determinations on a group of 28 rats during the dark (red light) period showed that cisternal amine metabolite concentrations before probenecid injection did not parallel turnover values. This was probably because individual differences in metabolite egress strongly affect the pre-probenecid values. The poor correlations between CSF tryptophan and 5-HT turnover suggested that differences of brain tryptophan concentration were not major determinants of differences of brain 5-HT metabolism within this group of normal rats. Considering that the rats were of similar weight and that the turnover values were all determined at approximately the same time of day, the three- to fourfold ranges of the turnover values are remarkable. The positive correlation between the DA and 5-HT turnovers of individual rats suggests the existence of common effects on DA and 5-HT turnover in normal rats.     

Neocortical Dialysate Monoamines of Rats After Acute, Subacute, and Chronic Liver Shunt

Abstract: Intracerebral microdialysis was applied to monitor the neocortical extracellular levels of the aromatic amino acids phenylalanine, tyrosine, and tryptophan, the neurotransmitters dopamine (DA), noradrenaline (NA), and serotonin (5-HT), and the metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole-3-acetic acid (5-HIAA) in rats with various forms of experimental hepatic encephalopathy (HE). The extracellular aromatic amino acid levels were clearly increased in acute, subacute, and chronic HE. No changes compared with controls in the neocortical DA release could be detected in the three experimental HE rat models investigated. The NA release showed a significant increase only in the subacute HE group. These data suggest that HE may not be associated with any major reduction of neocortical DA or NA release as previously suggested. In acute and subacute HE, decreased extracellular DOPAC but elevated 5-HIAA concentrations were seen. In chronic HE, elevations of both DOPAC and 5-HIAA were observed. Neocortical 5-HT release did not change in subacute and chronic HE, whereas it decreased in acute HE compared with control values. Significant increase in extracellular concentrations of 5-HIAA and of the 5-HIAA/5-HT ratio in the present study are in agreement with previously reported increases in 5-HT turnover in experimental HE. However, a substantially increased 5-HT turnover in experimental HE does not appear to be related to an increase in neuronal neocortical 5-HT release.     

Turnover rates of hypothalamic dopamine associated with the two types of prolactin surges during pseudopregnancy in rats.

Two surges of prolactin (PRL) are observed daily during pseudopregnancy (PSP) in the rat: the nocturnal (N) surge at dawn and the diurnal (D) surge in the evening. In order to clarify differences in the controlling mechanisms of the two types of PRL surges, we attempted to examine the turnover rates of dopamine (DA) and norepinephrine (NE) in the preoptic-anterior hypothalamus (PAH) and mid-posterior hypothalamus (MPH) on day 5-6 of PSP. The turnover rates of DA in the hypothalamus were inversely correlated with the serum PRL levels at the D surge when a significant increase in serum PRL was accompanied by not only a marked decrease in turnover rates of DA in the PAH, but also a slight decrease in turnover rates of the amine in the MPH. Contrarily, no significant decrease occurred in the turnover rates of DA in the hypothalamus at the N surge. There was no obvious correlation between the turnover rates of NE in the hypothalamus and the serum PRL levels at either PRL surge. These findings suggest that decreased turnover rates of DA in the hypothalamus are involved in the D surge, and it is most probable that the N PRL surge occurs under the control of another factor such as the hypothalamic PRL-releasing factor.     

Effect of aging on monoamines and their metabolites in the rat brain

Concentrations of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their acid merabolites were assayed in specific brain areas of Wistar rats of various ages. DA and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were significantly lower in striatum and mesolimbic areas of old (24 mos) rats than young adult (3 mos), but not mature (12 mos) rats. The decrease of homovanillic acid (HVA) was significant in mesolimbic areas but not in striatum. Neither cortical NE nor its metabolite methoxydroxyphenylglycol sulphate (MHPG-SO₄) were significantly changed by aging. 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the brainstem showed a tendency to a decrease and increase respectively in aged animals compared with young adults, but the differences were not statistically significant. However, the ratio of 5-HIAA to 5-HT concentrations was significantly higher in aged animals. The conclusion can be drawn that, in these brain areas, DA is more vulnerable to aging than NE and 5-HT, the metabolism of the latter being even enhanced.