Biogenic amine levels in the mid-term human fetus

Spectrophotofluorometric assays were used to measure concentrations of DA, NA, 5-HT and 5-HIAA present in extracts of brain tissue and CSF taken from midterm gestational fetuses of both sexes. The presence of biogenic amines was demonstrated in fetuses as early as 10.5 weeks gestation. In the hypothalamus, the concentrations (expressed in ng/100 mg tissue) ranged from 10.2 to 62.2 for NA, 11.6 to 258.8 for DA, 7.6 to 38.6 for 5-HT and 56.6 to 114.1 for 5-HIAA. Concentrations of DA and 5-HT were found to be significantly (P less than 0.05) higher in the hypothalamus than in the cortex, but those of NA and 5-HIAA were similar in both areas. No sex difference was observed. The concentrations of biogenic amines in the CSF (expressed in ng/ml) were 63.1-286.7 for NA, 43.2-108.1 for DA, 30.9-87.5 for 5-HT and 8.0-42.8 for 5-HIAA.     

Brain serotonin and catecholamine responses to repeated stress in rats

This study was designed to compare the effects of single and repeated administration of a discrete 2-min restraint stress on serotonin (5-HT) and catecholamine neuron activity in various regions of rat brain. A single 2-min restraint stress significantly increased the 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT responses in hypothalamus and cerebral cortex and the 5-HIAA response in brainstem. A second 2-min restraint stress applied 90 min after the initial stress did not appreciably alter the steady-state concentrations of 5-HIAA and 5-HT nor did it produce any further changes in the 5-HIAA and 5-HT responses compared to those seen following a single stress in these 3 brain regions. In addition, the synthesis rate of 5-HT in anterior hypothalamus, posterior hypothalamus, hippocampus and brainstem was not altered by a second stress applied 90 min after the initial stress. In contrast, a second 2-min restraint stress applied 30 or 60 min after the initial stress significantly increased the 5-HIAA concentration in hypothalamus, cerebral cortex and brainstem. Also, the synthesis rate of 5-HT was greater following application of a second stress at 30 min than following either a single stress or a second stress applied at 90 min. Following application of a single 2-min restraint stress the hypothalamic concentration of norepinephrine (NE) was significantly decreased at 5 min after onset of the stress and returned to prestress levels by 15 min; the hypothalamic dopamine (DA) concentration was significantly increased at 30 min after the onset of the stress, while the hypothalamic epinephrine (EPI) concentration remained unchanged. A second 2-min restraint stress applied at 30 min markedly lowered NE concentrations in whole and mediobasal hypothalamus but not in laterobasal hypothalamus, and the NE concentrations remained decreased for a period lasting at least 60 min; there was a significant decrease in the hypothalamic EPI concentration 60 min after application of the second stress at 30 min. In addition, the synthesis rate of catecholamines was significantly greater in anterior but not in posterior hypothalamus after application of a second stress 30 min after the initial stress than following either a single stress or a second stress applied at 90 min. Negative correlations were demonstrated between increased synthesis rates of both hypothalamic 5-HT and anterior hypothalamic catecholamines and decreased corticosterone response to single and repeated stress.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of neonatal rat Borna disease virus (BDV) infection on the postnatal development of the brain monoaminergic systems

Effects of neonatal Borna disease virus infection (BDV) on the postnatal development of brain monoaminergic systems in rats were studied. Tissue content of norepinephrine (NE), dopamine (DA) and its metabolite, 3,4-dihydroxyphenol acetic acid (DOPAC), and serotonin (5-HT) and its metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA) were assayed by means of HPLC-EC in frontal cortex, cerebellum, hippocampus, hypothalamus and striatum of neonatally BDV-infected and sham-inoculated male Lewis rats of 8, 14, 21, 60 and 90 days of age. Both NE and 5-HT concentrations were significantly affected by neonatal BDV infection. The cortical and cerebellar levels of NE and 5-HT were significantly greater in BDV-infected rats than control animals at postnatal days (PND) 60 and 90. Tissue content of NE in hippocampus was unaffected. In hippocampus, neonatally BDV-infected rats had lower 5-HT levels at PND 8 and significantly elevated levels at PND 21 and onwards. Neither striatal levels of 5-HT nor hypothalamic levels of 5-HT and NE were affected by neonatal BDV infection, suggesting that the monoamine systems in the prenatally maturing brain regions are less sensitive to effects of neonatal viral infection. 5-HIAA/5-HT ratio was not altered in BDV-infected rats indicating no changes in the 5-HT turnover in the brain regions damaged by the virus. Neither DA nor DOPAC/DA ratio was affected by neonatal BDV infection in any of the brain regions examined. The present data demonstrate significant and specific alterations in monoaminergic systems in neonatally BDV-infected rats. This pattern of changes is consistent with the previously reported behavioral abnormalities resulting from neonatal BDV infection.     

抑郁症患者自杀与脑脊液单胺代谢产物的关系

目的：探讨抑郁症患者自杀与脑脊液单胺代谢产物之间的关系。方法：应用高效液相色谱法，测定24例抑郁症患者(自杀组10例，无自杀组14例)及25例对照组5-羟色胺(5-HT)代谢产物5-羟吲哚乙酸(5-HIAA)，去甲肾上腺素(NE)代谢产物3-甲基-4-羟苯乙二醇(MHPG)及多巴胺(DA)代谢产物高香草酸(HVA)的浓度。结果：抑郁症自杀组5-HIAA浓度显著低于对照组，男性自杀组5-HIAA浓度、HVA浓度和HVA／MHPG比值均显著低于男性对照组，女性则无显著差异：结论：抑郁症患者自杀可能与5-HT和DA功能低下以及DA和NE之间的关系改变有关。     

Profile of NE, DA and 5-HT activity shifts in medial hypothalamus perfused by 2-DG and insulin in the sated or fasted rat

This study was carried out in the unrestrained rat to determine the nature of the in vivo profile of monoamine neurotransmitters within the medial hypothalamus in response to the presence of a glucoprivic or metabolic challenge to neurons within this region. In these experiments, insulin or 2-deoxy-D-glucose (2-DG) was applied locally to the paraventricular nucleus (PVN), dorsomedial nucleus (DMN) and ventromedial hypothalamus (VMH). In each of 11 Sprague-Dawley rats, a guide cannula was implanted stereotaxically to rest just above these structures. Upon recovery, a concentric push-pull cannula system was used to perfuse an artificial CSF within a medial hypothalamic site. The CSF was perfused at a rate of 20 microliters/min with a 5.0 min interval intervening between the collection of each 100 microliters sample. After the rat was fasted for 20-22 hr, either 10 micrograms/microliters 2-DG or 4.0 mU/microliters of insulin was incorporated into the control CSF medium and perfused at the same locus. The aliquots of hypothalamic perfusate were assayed by high performance liquid chromatography with electrochemical detection (HPLC-EC) for the respective concentration in pg/microliter of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and each of their major metabolic products. When the rat was sated, 2-DG enhanced significantly the mean efflux of NE from the medial hypothalamus in comparison to control CSF values. However, under the fasted condition, 2-DG augmented the turnover of both the catecholamine and 5-HT as reflected by elevated levels of MHPG and 5-HIAA, respectively. On the other hand, insulin perfused within the same medial hypothalamic sites evoked a significant increase in the synthesis and release of DA from the sated rat, but did not alter its turnover. Following the interval of fast, insulin produced no immediate alteration in transmitter activity; however, in the interval following insulin's perfusion, DA and 5-HT turnover were enhanced while the efflux of 5-HT was suppressed. An analysis of the proportional values of the levels of the amines to each other revealed marked shifts in the relationships between the catechol- and indoleamine transmitters following local perfusion with both 2-DG and insulin. Overall, NE synthesis and turnover exceeded that of 5-HT following 2-DG, whereas DA predominated over NE and 5-HT during insulin's perfusion.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of chronic nicotine administration on monoamine and monoamine metabolite concentrations in rat brain

The effects on rat brain tissue monoamine and monoamine metabolite concentrations of chronic nicotine administration at two doses (3 and 12 mg/kg/day) using constant infusion were studied. After 21 days of treatment, tissue concentrations of dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT), and several metabolites in striatum, hypothalamus, and frontal cortex were determined by high performance liquid chromatography with electrochemical detection. Compared with a control group, nicotine treatment significantly decreased NE in frontal cortex but not in other regions. The concentration of 5HT also was decreased in frontal cortex but increased in the hypothalamus at the higher dose of nicotine. The 5HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) was not significantly altered in any region. The 5HT index (5-HIAA/5-HT) was significantly decreased in the hypothalamus and increased in frontal cortex at the higher dose. Concentrations of DA and the metabolite homovanillic acid (HVA) were not significantly altered by nicotine. Nevertheless, significant decreases in the DA metabolite dihydroxyphenyl-acetic acid (DOPAC) were observed in both striatum and hypothalamus. Moreover, the DA index [(DOPAC + HVA)/DA] was significantly decreased in all three brain regions. In contrast to other studies using acute dose and in vitro perfusion paradigms that have reported increased CNS catecholamine release stimulated by nicotine, chronic administration appears to be associated with decreased catecholamine turnover in some brain regions.     

Brain monoaminergic and neuropeptidergic variations in human aging

Summary The effect of age on the monoamines 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA), their metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 3,4-dihydr-oxyphenylacetic acid (DOPAC), and the 5-HT precursor 5-hydroxy-L-tryptophan (5-HTP), together with the peptides neuropeptide Y (NPY), somatostatin (SOM), and corticotropin-releasing factor (CRF), was studied in frontal cortex, gyrus cinguli and hypothalamus from 23 healthy control subjects, aged 16–75 years. After correcting for postmortem interval, significant decreases in gyrus cinguli NA, NPY and CRF, and hypothalamic DA, HVA, and 5-HIAA concentrations were obtained with advancing age. The involvement of the monoaminergic system in several functional abnormalities appearing in senescence is suggested. Furthermore, evidence is given of the participation of the peptidergic systems in the aging process.     

Changes in cortical and subcortical levels of monoamines and their metabolites following unilateral ventrolateral cortical lesions in the rat

Suction lesions were made in the anterior, posterior or both halves of the right ventrolateral cortex in rats. Six days later, levels of the monoamine neurotransmitters, norepinephrine (NE), dopamine (DA) and serotonin (5-HT), and their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA), were measured in cortical and subcortical regions of lesioned rats and compared to values in sham-operated animals. NE and 5-HT were decreased in sections of ipsilateral (right) cortex including, and posterior to lesions, while 5-HIAA was increased throughout the ipsilateral cortex. Decreases in monoamines and increases in metabolites and metabolite:monoamine ratios (especially 5-HIAA:5-HT) were found in ipsilateral subcortical structures, including striatum, nucleus accumbens, hippocampus, hypothalamus, midbrain and brainstem, depending on the type of lesion. Subacutely, focal ventrolateral cortical lesions may profoundly alter the levels and utilization rates of monoamine neurotransmitters in widespread regions of the ipsilateral hemisphere.     

Analysis of temporal and dose-dependent effects of estrogen on monoamines in brain nuclei

Levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were measured in hypothalamic and limbic nuclei of ovariectomized rats after various doses of estradiol and at various intervals after estradiol administration. Of 13 areas examined, time- and dose-dependent effects of estrogen on monoamine content were restricted to only a few, discrete areas which concentrate estradiol. Subcutaneous administration of 1-50 micrograms of estradiol benzoate (EB) and measurement of monoamines 24 h later was associated with dose-dependent increases of NE in the medial preoptic nucleus, diagonal band nucleus and periventricular area of the anterior hypothalamus, and increased levels of DA in the periventricular area of the preoptic area. No changes were found in 5-HT levels, but dose-dependent increases in the level of the 5-HT metabolite, 5-hydroxyindole acetic acid (5-HIAA), were measured in the lateral portion of the ventromedial nucleus. Effects of 5 micrograms of EB were evaluated at 1.5, 6, 12 and 45 h after administration. No changes were noted at 1.5 h, but 5-HIAA in the ventromedial nucleus was elevated at 6 and 12 h. NE levels were elevated at 12 and 45 h in the diagonal band and preoptic nuclei and at 45 h in the lateral septum and periventricular area of the hypothalamus. DA levels decreased in the arcuate-median eminence area 45 h after estrogen. Intravenous administration of 10 micrograms of estrogen and measurement of monoamines 1 h later was not associated with altered levels of any monoamine suggesting that the estrogen-dependent changes are consistent with the genomic model for steroid hormone action.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebrospinal fluid (CSF) and brain monoamine metabolites in the developing rat pup

Concentrations of the neurotransmitters, serotonin (5-HT), dopamine (DA), and norepinephrine (NE) were measured in the developing rat brain at 12, 19, 26 and 42 days of age. The amino acid precursors, tryptophan (TRP) and tyrosine (TYR) were measured along with the 5-HT and DA metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), in brain and cerebrospinal fluid (CSF) at the above ages. This first report of CSF HVA levels in the developing rat shows that it, like 5-HIAA, declines with age. In contrast, the ontogeny of the compounds in brain are dissimilar, with 5-HIAA remaining relatively constant with age while HVA declines markedly. Possible reasons for the differences and similarities in the ontogeny of 5-HIAA and HVA levels in brain and CSF are discussed. The persistence of the ontogenetic pattern for the neurotransmitters and acid metabolites after central DA depletion is also reported.     

Gonadal influences on spinal cord and brain monoamines in male rats

Concentrations of norepinephrine (NE), dopamine (DA), 3,4-dihydroxy phenylacetic acid (DOPAC), serotonin (HT) and 5-hydroxyindoleacetic acid (HIAA) were measured by high-performance liquid chromatography-electrical detection (HPLC-ED) in homogenates of lumbosacral spinal cord, mediobasal hypothalamus and cerebral cortex of male rats. The effects of castration and testosterone propionate (TP) (20 micrograms/day X 2 days) were compared. Castrated animals had the highest levels of DA and DOPAC in the cerebral cortex and NE, HT and HIAA in the spinal cord, as well as decreased hypothalamic DOPAC. Testosterone treatment returned spinal cord monoamine concentrations to intact control levels. These findings point to the spinopetal monoaminergic pathways as sensitive targets for androgen action.     

Comparative effects of the neurotoxins N-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) and 6-hydroxydopamine on hypothalamic noradrenergic, dopaminergic and 5-hydroxytryptaminergic neurons in the male rat

The intracerebroventricular (i.c.v.) administration of 6-hydroxydopamine (6-OHDA; 50 micrograms X 3) and the systemic administration of DSP4 (50 mg/kg X 2; i.p.), alone and in combination, were compared for their abilities to alter the concentrations of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and 5-hydroxytryptamine (5-HT) in selected hypothalamic and extra-hypothalamic (striatum, frontal cortex, hippocampus) regions of the male rat brain. DSP4 markedly lowered NE concentrations in extrahypothalamic regions, and within the hypothalamus produced a mild and variable reduction of NE without altering concentrations of DA, DOPAC or 5-HT. 6-OHDA markedly lowered NE concentrations in all brain regions, but was without effect on DA, DOPAC and 5-HT concentrations in any region analyzed. Combined treatment with DSP4 and 6-OHDA did not produce additional effects on levels of NE, DA and DOPAC over either drug alone, but did cause a mild reduction of 5-HT in several brain regions. These results indicate that systemic treatments with DSP4 per se are not as effective as i.c.v. 6-OHDA in depleting NE in the hypothalamus, and that when the two neurotoxins are administered there appears to be some destruction of 5-HT neurons.     

Effects of blinding and pinealectomy on regional brain monoamine concentrations

The effects of blinding with or without pineal ablation on brain monoamine levels were studied in male rats. Brain dopamine (DA), norepinephrine (NE), epinephrine (E), and serotonin (5-HT) were measured by radioenzymatic assays. Four weeks following pinealectomy, E levels were significantly enhanced in the frontal cortex. Chronic blinding decreased striatal DA levels and increased striatal 5-HT levels in both sham-operated and pinealectomized (Px) animals. In a second experiment Px animals were sacrificed 1 or 7 d after pinealectomy in order to examine the short-term effects of pinealectomy. There were no differences between controls and Px animals in their cortical levels of DA, NE, and E and their hippocampal and hypothalamic 5-HT levels. However, the E concentrations measured 1 d after surgery were significantly greater than after 7 d. The implications of these findings with regard to the reported role of the pineal and melatonin in brain homeostasis and endocrine regulation are discussed.     

Late changes in cerebral monoamine metabolism following focal ventrolateral cerebrocortical lesions in rats

Twelve weeks after focal ventrolateral cerebrocortical suction lesions (ca. 12 X 4 mm) were made in rats, concentrations of the monoamines norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and their metabolites were measured in several cortical and subcortical brain regions using high performance liquid chromatography with electrochemical detection. Widespread changes in the concentrations of monoamines, their metabolites, and metabolite:monoamine ratios were found in the hemisphere ipsilateral to unilateral (right) lesions, and bilaterally in animals with bilateral lesions. NE was decreased in undamaged dorsolateral cortex and hippocampus, and tended to be increased in striatum and midbrain ipsilateral to lesions. DA was increased in the hypothalamus of bilaterally lesioned animals, and also tended to be increased in striatum and midbrain. The changes of greatest magnitude and anatomical extent were found in the serotonin system: 5-HT was generally increased, and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HIAA:5-HT ratio were decreased throughout the cerebral hemispheres ipsilateral to lesions. These widespread changes in cerebral 5-HT metabolism were qualitatively different and smaller than those previously found at 6 days after cortical lesions, and suggest a biphasic response of the ipsilateral 5-HT system to ventrolateral cortical injury.     

Brain regional levels of neurotransmitter amines as neurochemical correlates of sex-specific ontogenesis in the rat.

Brain regional levels of three neurotransmitter amines - serotonin (5-HT), norepinephrine (NE), dopamine (DA) - were measured in young rats prior to weaning to determine the extent to which modifications in levels of amines might reflect alterations in the sex steroid hormonal environment during the first postnatal week in the life of the rat. Sex-related levels of DA, NE, and 5-HT were found in some brain regions of the 12-day-old rat. Male midbrain DA exceeded the corresponding female value while female hypothalamic NE levels were greater than those of the male. Levels of 5-HT in the corpus striatum and the midbrain of males were greater than those of the female. Castration of the male on day 1 or testosterone propionate (TP) administration to the newborn female resulted in modifications of levels of midbrain 5-HT which reflected feminization of the castrated males and masculinization of the TP-treated females. Castration on day 1, or diethylstilbestrol given on days 2, 4, and 6, resulted in apparent feminization of NE levels in the hypothalamus of 12-day-old male rats. Thus, it appears that regional levels of hypothalamic NE and midbrain 5-HT in the 12-day-old rat may reflect the course of brain organizational activity which becomes recognizable in the adult as sex-specific behavior.     

Modification of gonadectomy-induced increases in brain monoamine metabolism by steroid hormones in male and female rats

Concentrations of monoamines (dopamine, DA; serotonin, 5-HT) and their major metabolites (homovanillic acid — HVA; dihydroxyphenylacetic acid — DOPAC; 5-hydroxyindolacetic acid — 5-HIAA) were measured in selected brain areas of chronically gonadectomized, steroid- or oil-treated male and female rats. Concentrations of DOPAC and HVA were markedly increased in the hypothalamus (male, female), striatum (male, female) and brainstem (male) following gonadectomy, whereas the levels of DA remained unaltered in most of the brain areas examined. Most of the changes were reversed or attenuated by chronic estradiol (EB) substitution. In contrast, chronic treatment with physiological concentrations of testosterone (TP) reduced indexes of DA turnover only in the striatum of ovariectomized (OVX) and brainstem of orchidectomized (ORDX) rats. ORDX-related increases in striatal levels of DOPAC and HVA were not reversed by either EB or TP. ORDX increased the levels of 5-HIAA (hypothalamus, striatum) and decreased those of 5-HT (hypothalamus, hippocampus). These changes were reversed by chronic treatment with either TP or EB. Brain metabolism of 5-HT remained unaltered following OVX.

Gonadectomy and chronic steroid replacement therapy appear to alter brain monoamine metabolism in a brain region and sex-dependent manner. Our data demonstrate that gonadectomy-related increases in the activity of brain monoaminergic neurons in both male and female rats was attenuated more effectively with physiological concentrations of estradiol than with testosterone. Insensitivity of monoaminergic neurons in a number of brain areas (e.g., hypothalamus, striatum) to the action of testosterone was evident in both sexes.     

Effects of ketamine on dopamine metabolism during anesthesia in discrete brain regions in mice: comparison with the effects during the recovery and subanesthetic phases

The effects of ketamine on the levels of dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT, serotonin) and their metabolites were examined in discrete brain regions in mice. A high dose of ketamine (150 mg/kg, i.p.) did not change DA metabolism in the frontal cortex, nucleus accumbens, striatum and hippocampus, but did decrease it in the brainstem during anesthesia. In contrast, during recovery from the ketamine anesthesia, the high dose increased the level of homovanillic acid (HVA) in all brain regions. A low subanesthetic dose of ketamine (30 mg/kg, i.p.) increased the concentrations of both 3,4-dihydroxyphenylacetic acid (DOPAC) and HVA only in the nucleus accumbens. The DA level was not affected by any ketamine treatment. During ketamine anesthesia, the content of 3-methoxy-4-hydroxy-phenylglycol (MHPG) was decreased in the brainstem, whereas during recovery from anesthesia, the MHPG level was increased in the frontal cortex, nucleus accumbens and brainstem. The NE content was not altered in any region by ketamine treatment. The concentration of 5-hydroxyindoleacetic acid (5-HIAA) was reduced in the frontal cortex, striatum, hippocampus and brainstem during ketamine anesthesia. The 5-HT level was unaltered in all regions except the brainstem where it was reduced. In contrast, after anesthesia, the concentrations of both 5-HT and 5-HIAA were increased in the striatum. During the subanesthetic phase, however, the levels of NE, 5-HT and their metabolites were unchanged. These neurochemical results are consistent with the electrophysiological findings that a high dose of ketamine does not change the basal firing rates of nigrostriatal DA neurons during anesthesia, while low subanesthetic doses significantly increase those of ventral tegmental DA neurons.     

Endotoxin administration stimulates cerebral catecholamine release in freely moving rats as assessed by microdialysis

In vivo microdialysis was used to measure changes in extracellular concentrations of catecholamines and indolamines in freely moving rats in response to administration of endotoxin (lipopolysaccharide, LPS). Dialysis probes were placed stereotaxically in either the medial hypothalamus or the medial prefrontal cortex. We used a repeated-measures design in which each rat received LPS or saline, and each subject was retested with the other treatment one week later. With the dialysis probes in the medial hypothalamus, intraperitoneal (ip) administration of LPS (5 μg) increased dialysate concentrations of norepinephrine (NE, 187%), dopamine (DA, 119%), and all their measured catabolites, except normetanephrine. Dialysate concentrations of NE and DA were elevated significantly in the fourth or fifth (20 min) collection period with a peak response at around 2 hr. They returned to baseline by about 4 hr. When the dialysis probes were placed in the medial prefrontal cortex, the same dose of LPS also elevated dialysate concentrations of NE and DA, but the increases were much smaller (ca. 20%). However, a dose of 100 μg LPS increased dialysate concentrations of NE and DA from the medial prefrontal cortex to an extent comparable to that of the 5 μg dose in the hypothalamus, and the response was more prolonged. Dialysate concentrations of serotonin could not be measured reliably, but those of its catabolite, 5-hydroxyindoleacetic acid (5-HIAA), were also elevated in both regions. The peak of 5-HIAA occurred at around 4 hr. Pretreatment of the rats with indomethacin (10 mg/kg ip) completely prevented the changes due to 100 μg LPS in the medial prefrontal cortex. These results support earlier neurochemical data suggesting that LPS stimulates the release of both DA and NE in the brain, and probably also release of serotonin. © 1995 Wiley-Liss, Inc.     

Modulatory Effects of Melatonin on Cadmium-Induced Changes in Biogenic Amines in Rat Hypothalamus

This study was undertaken to examine whether cadmium oral exposure modifies biogenic amine concentration at hypothalamic level in adult male rats, and to investigate the possible modulatory effects of melatonin against cadmium-induced changes on these neurotransmitters. For this purpose, rats were exposed to cadmium (25 mg/l of CdCl₂ in the drinking water) with or without melatonin (30 μg/rat/day intraperitoneally) for 30 days. Norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3,4-dihydroxyphenyl acetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were quantified by high performance liquid chromatography (HPLC). Oral cadmium administration led to decrease of NE, DA, and 5-HT content and DA turnover within the three hypothalamic regions examined, and therefore an inhibition of 5-HT turnover at posterior hypothalamus. Sensitivity to melatonin was specific to the hypothalamic region evaluated. Thus, the anterior hypothalamus was not nearly sensitive to exogenously administered melatonin, whereas the neurohormone decreased the content of these amines in the mediobasal hypothalamus, and melatonin increased it in the posterior hypothalamic region. Melatonin effectively prevented some cadmium-induced alterations on hypothalamic amine concentration. This is the case of DA in the anterior and posterior hypothalamus, and 5-HT metabolism in the posterior hypothalamic region. In conclusion, the obtained results indicate that melatonin treatment may be effective modulating some neurotoxic effects induced by cadmium exposure, and, more to the point, a possible role of this indolamine as a preventive agent for environmental or occupational cadmium contamination.     

Rat brain hypothalamic and hippocampal monoamine and hippocampal beta-adrenergic receptor changes during pregnancy.

The concentration of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites was measured in hypothalamic and hippocampal brain tissue obtained from non-pregnant, 15- or 20-day pregnant and 4-day postpartum rats. At 20 days of pregnancy, hypothalamic NA and DA concentrations were significantly decreased and their turnover increased relative to postpartum and estrous values, respectively. Hippocampal 3-methoxy-4-hydroxy-phenylglycol (MHPG) levels were significantly decreased at 15 days of pregnancy and 4 days postpartum compared to estrous and 20-day pregnant levels and the MHPG/NA ratio was significantly reduced at 4 days postpartum relative to the estrous value. Hippocampal 5-HT and 5-hydroxyindole-3-acetic acid (5-HIAA) levels were significantly decreased at 15 days of pregnancy while 5-HIAA levels and the 5-HIAA/5-HT ratio were significantly decreased at 20 days of pregnancy. Hippocampal beta-adrenergic receptor density was significantly lower at 4 days postpartum than at 15 days of pregnancy. A positive correlation was observed between plasma progesterone and hippocampal beta-adrenoceptor Kd values, suggesting a possible causal relationship between these two variables. The monoamine and beta-adrenoceptor changes which occur during pregnancy may be an important contributing factor in determining the mood changes which occur during pregnancy and postpartum.