Twenty-four-Hour Rhythms of Serum Acth,Prolactin, Growth Hormone,and Thyroid-Stimulating Hormone,and of Median-Eminence Norepinephrine,Dopamine, and Serotonin,in Rats Injected with Freund's Adjuvant

The effect of Freund's adjuvant injection on 24-h variation of circulating ACTH, prolactin, growth hormone (GH), and thyroid-stimulating hormone (TSH) levels, and of norepinephrine (NE) content, and dopamine (DA) and serotonin (5HT) turnover in median eminence, was examined in adult rats kept under light between 0800 and 2000 h daily. Groups of 6–10 animals Freund's complete adjuvant or its vehicle at 1 lOOh 3 days before sacrifice and were killed by decapitation at six different time intervals throughout a 24-h cycle. In rats injected with adjuvant's vehicle, serum ACTH and prolactin exhibited peak values around the light-dark transition (p < 0.0001 and < 0.04, respectively), while the maximum in TSH was found in the late afternoon (p < 0.0001, one-way ANOVA). GH levels did not vary on a 24-h basis. In Freund's adjuvant-injected rats, 24-h variations of TSH levels became blunted, while 24-h variations of prolactin and ACTH persisted. Freund's adjuvant augmented serum ACTH and prolactin levels, and decreased GH and TSH levels (p < 0.0007, factorial ANOVA). Median-eminence NE content, and turnover of DA, assessed by measuring dihydroxyphenylacetic acid, DOPAC/DA ratio, and of 5HT, assessed by measuring 5-hydroxyindoleacetic acid, HIAA/5HT ratio, varied on a 24-h basis in rats receiving adjuvant's vehicle (p < 0.02). Median-eminence NE content attained its maximum at 1600–2000 h, while maxima in DOPA/DA and HIAA/5HT ratios occurred at 0400 h. Injection with Freund's adjuvant reduced the amplitude of the daily variation of NE content, shifted the maximum of DOPAC/DA ratio toward the light-dark transition, and blunted the daily variation in HIAA/5HT ratio in median eminence. The administration at 1200 of the immunosuppressant drug cyclosporine (5 mg/kg, 5 days) restored the augmented ACTH and prolactin levels (p < 0.0001, factorial ANOVA) and depressed GH and TSH levels (p < 0.02) found in Freund's adjuvant-injected rats. Cyclosporine was also effective in restoring 24-h rhythmicity of serum ACTH and TSH, but not of prolactin, levels. Cyclosporine did not modify the effect of Freund's adjuvant on time-of-day changes of median-eminence NE content, but it was effective in counteracting the changes of DA and 5HT turnover found after immunization. The results are compatible with a significant effect of immune-mediated inflammatory response at an early phase after Freund's adjuvant injection on ACTH, GH, prolactin, and TSH release, which is partially sensitive to immunosuppression by cyclosporine. (Chronobiology International, 14(3), 253–265, 1997)     

Effects of Chronic Restraint Stress on Feeding Behavior and on Monoamine Levels in Different Brain Structures in Rats

Monoaminergic systems are important modulators of the responses to stress. Stress may influence feeding behavior, and the involvement of monoamines in the control of food intake is well recognized. We investigated the effects induced by chronic-restraint stress, 1 h a day, for 40 days, on eating behavior and on monoamines in distinct brain structures. Increased consumption of sweet pellets, and not of peanuts, was observed. Dopamine (DA), serotonin (5–HT), and their metabolites were measured by HPLC-EC. After chronic restraint, the results observed were decreased 5–HT in hippocampus, with increased 5–HIAA/5–HT; decreased 5–HIAA levels in cortex; reduction in DA in hippocampus, and increased levels in amygdala and hypothalamus; HVA increased in cortex, as well as HVA/DA ratio, while DOPAC/DA decreased. HVA decreased in hypothalamus, as well as HVA/DA, and DOPAC/DA and HVA/DA decreased in the amygdala. These results suggest that restraint stress differentially affects the activity of central dopaminergic and serotonergic neurons, and this may be related to the effects observed in eating behavior.     

Melatonin synthesis in the optic lobes and midbrain of the grasshopper Oedipoda caerulescens

The pathways of insect melatonin (MEL) biosynthesis apparently follow the same routes as those identified in vertebrates but information on MEL synthesis variations related with serotonin (5‐HT), 5‐hydroxy‐indole acetic acid (5HIAA), and N‐acetylserotonin (NAS) levels, as well as 5‐HT N‐acetyltransferase (NAT) activity throughout the day, is very limited in the insect nervous system. In the present study, the levels of MEL, metabolites (5‐HT, NAS, and 5‐HIAA) and enzyme NAT were determined in the optic lobes and the midbrain of the grasshopper Oedipoda caerulescens, in conditions of light and darkness. In both tissues, a different pattern of MEL synthesis was observed over the light/dark cycle. Variations in the levels of 5‐HT, NAS and NAT activity related to the synthesis of cerebral MEL follow a pattern very similar to that observed in the pineal of mammals, with a peak of synthesis in the first half of the scotophase. Also, we observed differences in the metabolism of 5‐HT between the optic lobes and the midbrain light/dark‐dependent.     

腺苷受体拮抗剂对帕金森病小鼠神经递质的影响

运用神经毒剂ＭＰＴＰ（１－ｍｅｔｈｙ－４－ｐｈｅｎｙ－１,２,３,６－ｔｅｔｒａｈｙｄｒｏｐｙｒｉｄｉｎｅ）制作的ＩＣＲ小鼠帕金森病模型,通过荧光测定方法和免疫组织化学方法,测定ＭＰＴＰ及腺甘Ａ２ａ受体拮抗剂喹唑啉（Ｑｕｉｎａｚｏｌｉｎｅ,ＣＰ６６７１３）对单胺类神经递质去甲肾上腺素（ＮＡ）、多巴胺（ＤＡ）、５－羟色胺（５－ＨＴ）及其代谢产物５－羟吲哚乙酸（５－ＨＩＡＡ）和氨基酸类神经递质γ－氨基     

Prenatal Exposure to Ozone Disrupts Cerebellar Monoamine Contents in Newborn Rats

Ozone (O3) is widely distributed in environments with high levels of air pollution. Since cerebellar morphologic disruptions have been reported with prenatal O3 exposure, O3 may have an effect on some neurotransmitter systems, such as monoamines. In order to test this hypothesis, we used 60 male rats taken from either, mothers exposed to 1 ppm of O3 during the entire pregnancy, or from mothers breathing filtered and clean air during pregnancy. The cerebellum was extracted at 0, 5, and 10 postnatal days. Tissues were processed in order to analyze by HPLC, dopamine (DA) levels, 3,4 dihydroxyphenilacetic acid (DOPAC) and homovanillic acid (HVA), norepinephrine (NA), serotonin, and 5-hydroxy-indole-acetic acid (5-HIAA) contents. Results showed a decrease of DA, NA, DOPAC and HVA mainly in 0 and 5 postnatal days. There were no changes in 5-HT levels, and 5-HIAA showed an increase after 10 postnatal days. DOPAC + HVA/DA ratio showed changes in 0 and 10 postnatal days, while 5-HIAA/5-HT ratio showed a slight decrease in 0 days. The data suggest that prenatal O3 exposure disrupts the cerebellar catecholamine system rather than the indole-amine system. Disruptions in cerebellar NA could lead to ataxic symptoms and also could limit recovery after cortical brain damage in adults. These finding are important given that recovery mechanisms observed in animals are also observed in humans.     

Effects of acute and prolonged naphthalene exposure on brain monoaminergic neurotransmitters in rainbow trout (Oncorhynchus mykiss)

We have shown previously that acute (1 to 6 h) and prolonged (1 to 5 days) exposure of rainbow trout to naphthalene resulted in decreased plasmatic cortisol and 17-beta-estradiol levels. In order to elucidate the mechanisms through which naphthalene might disrupt endocrine regulation, the present study investigated whether brain monoaminergic neurotransmitters are altered by the action of this polycyclic aromatic hydrocarbon. In a first experiment, immature rainbow trout were injected with vegetable oil alone or containing naphthalene (10 and 50 mg/kg, i.p.), and sacrificed 1, 3 and 6 h after treatment. In a second experiment, slow-coconut oil implants alone or containing naphthalene (doses of 10 and 50 mg/kg) were i.p. located and fish sacrificed 1, 3 and 5 days after treatment. Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline (NA) were measured in several brain regions by HPLC. The results show that short-term naphthalene increases DA and 5-HT contents in hypothalamus and telencephalon, but differentially alter contents of the acid metabolites. Implants with naphthalene reduced DA content in hypothalamus and preoptic region but increased in telencephalon. 5-HT metabolism was decreased in hypothalamus, preoptic region, pituitary and brain stem after 3 to 6 days of treatment. In addition, the levels of NA were increased in hypothalamus and telencephalon after acute treatment and in hypothalamus and preoptic area after several days of exposure to naphthalene. These data suggest that brain neurotransmitter systems are sensitive to polycyclic aromatic hydrocarbons and could represent a target of the naphthalene-induced neuroendocrine disruption.     

Brain Monoamine Changes in Rats After Short Periods of Ozone Exposure

We have shown in our laboratory that cat's and rat's sleep disturbances are produced by 24 h of ozone (O₃) exposure, indicating that the central nervous system is affected by this gas. To demonstrate the probable changes in brain neurotransmitters, we evaluated the monoamine contents of the midbrain and striatum of rats exposed to 1 part per million O₃ for 1 or 3 hours periods. The results were compared with rats exposed to fresh air and to those exposed to 3 hours of O₃ followed by 1 or 3 hours of fresh air. We found a significant increase in dopamine (DA) and its metabolites noradrenaline (NA) and 3,4 dihydroxyphenylacetic acid (DOPAC), as well as an increase in the 5-hydroxyindolacetic acid (5-HIAA) contents of the striatum. There were no changes in homovanillic acid (HVA) and serotonin (5-HT) levels during O₃ exposure. Additionally, an increase in DA, NA and 5-HIAA in the midbrain during O₃ exposure was observed. Turnover analysis revealed that DA increased more than its metabolites in both the midbrain and striatum. However, the metabolite of 5-HT, i.e. 5-HIAA, increased more than its precursor, this reaching statistical significance only in the midbrain. These findings demonstrate that O₃ or its reaction products affect the metabolism of major neurotransmitter systems as rapidly as after 1 h of exposition.     

Serotonin,dopamine, noradrenaline and their metabolites: Levels in the brain of the house cricket (Acheta domesticus L.) during a 24-hour period and after administration of quipazine—a 5-HT2 receptor agonist

1. The levels of 5-HT, DA, NA and DA metabolites (NADA, DOPAC) measured by HPLC (with electrochemical detection) in the brain of the house cricket did not change over a 24-hr period. The level of 5-HIAA, a 5-HT metabolite, was below the limit of detection.2. The 5-HT and DOPAC levels decreased and NADA increased after quipazine injection but DA and NA levels did not change after it.3. [³H]Ketanserin was used to identify serotonin receptors bound to sites in the house cricket brain with a K_d of 5 nM and a concentration of B_max 180 fmol/mg protein.     

Rat brain monoamine and serotonin S2 receptor changes during pregnancy

The concentrations of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites were determined in 5 brain areas of non-pregnant, 15 and 20 day pregnant and 4 day post-partum rats. Striatal 5-HT content was significantly lower in 15 and 20 day pregnant rats than in estrous controls. A significant decrease in striatal and frontal cortex 5-hydroxyindole-3-acetic acid (5-HIAA) concentration was observed in 15 day pregnant rats. Significant increases in hypothalamic and hippocampal NA levels were observed at 4 days post-partum. Frontal cortex serotonin S2 receptorKd was reduced in 4 day post-partum rats. There was no significant change in S2 receptorB _max during pregnancy. Levels of progesterone were negatively correlated with striatal DA, homovanillic acid (HVA), 5-HT, and 5-HIAA levels, hypothalamic DA, hippocampal 5-HT, and frontal cortex 5-HIAA values as well as striatal HVA to DA, and HVA to 3,4-dihydroxyphenylacetic acid (DOPAC) ratios and amygdaloid HVA to DOPAC ratios. The limbic neurotransmitter changes might possibly contribute to mood changes which occur during pregnancy and post-partum.     

Physical training prevents oxidative stress in L‐NAME‐induced hypertension rats

The present study investigated the effects of a 6‐week swimming training on blood pressure, nitric oxide (NO) levels and oxidative stress parameters such as protein and lipid oxidation, antioxidant enzyme activity and endogenous non‐enzymatic antioxidant content in kidney and circulating fluids, as well as on serum biochemical parameters (cholesterol, triglycerides, urea and creatinine) from Nω‐nitro‐L‐arginine methyl ester hydrochloride (L‐NAME)‐induced hypertension treated rats. Animals were divided into four groups (n = 10): Control, Exercise, L‐NAME and Exercise L‐NAME. Results showed that exercise prevented a decrease in NO levels in hypertensive rats (P < 0·05). An increase in protein and lipid oxidation observed in the L‐NAME‐treated group was reverted by physical training in serum from the Exercise L‐NAME group (P < 0·05). A decrease in the catalase (CAT) and superoxide dismutase (SOD) activities in the L‐NAME group was observed when compared with normotensive groups (P < 0·05). In kidney, exercise significantly augmented the CAT and SOD activities in the Exercise L‐NAME group when compared with the L‐NAME group (P < 0·05). There was a decrease in the non‐protein thiols (NPSH) levels in the L‐NAME‐treated group when compared with the normotensive groups (P < 0·05). In the Exercise L‐NAME group, there was an increase in NPSH levels when compared with the L‐NAME group (P < 0·05). The elevation in serum cholesterol, triglycerides, urea and creatinine levels observed in the L‐NAME group were reverted to levels close to normal by exercise in the Exercise L‐NAME group (P < 0·05). Exercise training had hypotensive effect, reducing blood pressure in the Exercise L‐NAME group (P < 0·05). These findings suggest that physical training could have a protector effect against oxidative damage and renal injury caused by hypertension. Copyright © 2012 John Wiley & Sons, Ltd.     

Effects of holding temperature and handling stress on the upper thermal tolerance of threadfin shad Dorosoma petenense

The critical thermal maxima (T_MAX) of threadfin shad Dorosoma petenense exposed to standardized stress (30 s handling in a dip‐net), simulating stressors endured during fish loading before transport, were measured over a range of holding temperatures (15, 20 and 25° C). Dorosoma petenense T_MAX showed a significant thermal effect, displaying mean ±s.d . critical thermal maxima of 26·5 ± 1·6, 30·9 ± 1·2 and 33·3 ± 1·4° C, when tested at temperatures of 15, 20 and 25° C, respectively. Dorosoma petenense T_MAX levels were also affected by stress, with handled fish showing significantly lower values than control fish exposed to 15 (mean ±s.d . T_MAX = 25·6 ± 2·0° C), 20 (27·6 ± 2·8° C) and 25° C (32·0 ± 2·6° C). In addition to providing basic information on D. petenense thermal tolerance, experimental results suggest that fishery managers should consider the whole suite of potential stressors, such as air exposure during handling and fish loading, when developing management criteria.     

Stereoselective effect of kynurenine enantiomers on the excretion of serotonin and its metabolite in rat urine

A solution of optically pure kynurenine (KYN), i.e., D ‐KYN or L ‐KYN, was administered intravenously to male Sprague‐Dawley rats (10 mg kg^?1 ml^?1). The time‐course of changes in the concentrations of urinary monoamines and their metabolites such as 5‐hydroxytryptamine (5‐HT), 5‐hydroxyindole acetic acid (5‐HIAA), dopamine, and 3‐methoxytyramine were investigated by reversed‐phase high‐performance liquid chromatography with electrochemical detection after precolumn derivatization with (2R)‐2,5‐dioxopyrrolidin‐1‐yl‐2,5,7,8‐tetramethyl‐6‐(tetrahydro‐2H‐pyran‐2‐yloxy)chroman‐2‐carboxylate (NPCA). We observed a stereoselective difference in the effects of the KYN enantiomers. Only D ‐KYN, not L ‐KYN, caused a significant increase in urinary 5‐HT levels within 30 min after its administration. With regard to the metabolites, urinary 3‐MT level was increased by D ‐KYN administration. On the other hand, no significant change in the DA level was observed after administration of either D ‐KYN or L ‐KYN. These results suggest that D ‐KYN could affect the activity of neuroactive amines, especially 5‐HT, in vivo. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

The late stage following continuous amphetamine administration to rats is correlated with altered dopamine but not serotonin metabolism

In previous experiments rats pretreated with slow-release d-amphetamine (d-Amp) pellets for $\text{4}\text{1}\text{2}$ days, given a 12-hr drug-free period, and then injected with d-Amp have been found to show a behavioral syndrome which has similarities to that induced by acute injections of the hallucinogens LSD and mescaline. The present results indicate that rats administered this same drug regimen have large decreases in Dopamine (DA), dihydroxyphenyl acetic acid (Dopac), and homovanillic acid (HVA) in caudate nucleus, smaller decreases in DA with no changes in Dopac and HVA levels in nucleus accumbens, but no alterations in 5-hydroxytryptamine (5HT) and 5-hydroxyindole acetic acid (5HIAA) levels in caudate, accumbens, brainstem and hippocampus. Increased 5HIAA levels are found in rats sacrificed with pellets intact following 3 days of continuous d-Amp administration, while sleep deprived and in motor stereotypies. The late and hallucinatory stage following continuous d-amp is correlated more closely with alterations in dopamine than of 5HT.     

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice is enhanced by ethanol or acetaldehyde

Persistent neurochemical changes consistent with parkinsonism have been reported in brains of mice treated with repeated high doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We now report that ethanol or acetaldehyde potentiate MPTP-induced damage to mouse striatum. One hour after the combined treatments (ethanol and MPTP or acetaldehyde and MPTP), the animals exhibited a marked and long-lasting catatonic posture and then returned gradually to apparently normal locomotion. Seven days after MPTP administration, depletion of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in mouse striatum were further potentiated in the group of animals treated with ethanol. This effect was more evident when the treatment was repeated twice and was dose-dependent. Acetaldehyde was more potent than ethanol in enhancing MPTP neurotoxicity. A single exposure to acetaldehyde before and during MPTP treatment produced a very consistent fall of DA, DOPAC and HVA but not serotonin (5HT) or 5-hydroxyindoleacetic acid (5HIAA) in the striatum. This suggests that ethanol effects on MPTP neurotoxicity might be related to acetaldehyde formation.     

Increased Cerebrospinal Fluid Dopamine and 3,4-Dihydroxyphenylacetic Acid Levels in Huntington''s Disease: Evidence for an Overactive Dopaminergic Brain Transmission

Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) in the CSF of patients with Huntington's disease (HD) were measured by HPLC. CSF DA, DOPAC, and MHPG levels were found to be increased in HD patients. Levels of HVA, 5-HIAA, and NA in the CSF of HD patients did not differ from those of controls. Changes in CSF DA and DOPAC levels were consistent with previous findings of increased DA tissue content in some brain areas of patients with HD. These results suggest that CSF DOPAC levels could be a more reliable index of overactive dopaminergic brain systems in HD than CSF HVA levels.     

Regional Variations of 5HT Concentrations in Rora sg (staggerer) Mutants

Ataxic Rora ^sg (staggerer) mouse mutants, containing a deletion of the Rora gene which encodes a retinoid-like nuclear receptor, were compared to non-ataxic controls for concentrations of 5-hydroxytryptamine (HT), its main metabolite (5-hydroxy-indole acetic acid, 5HIAA), and its precursor (tryptophan) in cerebellum, brainstem, and forebrain. In Rora ^sg cerebellum, 5HT concentrations increased relative to controls, while tryptophan concentrations decreased. 5HIAA concentrations increased in mutant cerebellum and brainstem, but the 5HIAA/5HT ratio declined only in cerebellum. These results indicate that 5HT turnover decreased in cerebellum of an ataxic mutant, perhaps indicative of presynaptic accumulation and compromised neurotransmission and susceptible to be modified by 5HT pharmacotherapy.     

Characterization of D2 receptors and dopamine levels in the thalamus of the rat.

We kinetically characterized D2 receptors in thalami pooled from a group of Sprague-Dawley rats and then determined thalamic levels of dopamine (DA), homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), and norepinephrine (NE) in relation to a measure of thalamic DA D2 receptor densities in another group of rats. The equilibrium dissociation constant (kd) was estimated as 0.1 nM by three independent methods, while the Bmax for thalamic D2 receptors was found to be 6.4 fmol/mg p using 3H-spiperone as ligand and ketanserin to occlude 5HT2 binding. Kinetic constants were in agreement with previously reported kinetic data from rodent caudate-putamen. This suggests that thalamic D2 receptors are similar to D2 receptors from other brain areas. Mean thalamic levels of DA (22.6 ng/mg p), DOPAC (1.19 ng/mg p) and HVA (0.31 ng/mg p) concur with previous reports of a sparse distribution of thalamic DA neurons. D2 receptor densities were positively correlated with DA metabolites DOPAC (P less than .05; r = 0.423) and HVA (P less than .05; r = 0.368), but not DA or NE. These results establish fundamental characteristics of thalamic DA neurotransmission to assist in the investigation of behavioral pharmacology of this area.     

Triploidy alters brain morphology in pre‐smolt Atlantic salmon Salmo salar: possible implications for behaviour

Total brain mass and the volumes of five specific brain regions in diploid and triploid Atlantic salmon Salmo salar pre‐smolts were measured using digital images. There were no significant differences (P > 0·05) in total brain mass when corrected for fork length, or the volumes of the optic tecta or hypothalamus when corrected for brain mass, between diploids and triploids. There was a significant effect (P < 0·01) of ploidy on the volume of the olfactory bulb, with it being 9·0% larger in diploids compared with triploids. The cerebellum and telencephalon, however, were significantly larger, 17 and 8% respectively, in triploids compared with diploids. Sex had no significant effect (P > 0·05) on total brain mass or the volumes of any measured brain region. As the olfactory bulbs, cerebellum and telencephalon are implicated in a number of functions, including foraging ability, aggression and spatial cognition, these results may explain some of the behavioural differences previously reported between diploids and triploids.     

Changes in rat brain monoamine turnover following chronic antidepressant administration

Changes in rat brain monoamine turnover were studied following the chronic administration of five agents which markedly differ in their patterns of monoamine uptake inhibition. Compounds (10 mg/kg, i.p.) were injected once daily for 14 days and experiments undertaken 24 h after the last injection. Chronic administration of desipramine or mianserin elevated brain MOPEG-SO₄ content and the α-MT-induced reduction in brain NA levels was enhanced by chronic desipramine. either antidepressant altered turnover of brain DA or 5-HT. Steady state levels of brain 5-HIAA or striatal levels of DOPAC or HVA were also unchanged. Chronically administered Org 6582, a selective inhibitor of 5-HT uptake, decreased basal and attenuated the probenecid-induced increase iin brain 5-HIAA levels. Chronic Org 6582 had no effect on NA or DA turnover and on the levels of MOPEG-SO₄, DOPAC or HVA. Neither maprotiline nor chlorimipramine altered turnover of NA, DA or 5-HT or levels of metabolites. Thus, in contrast to the acute situation, chronically administered desipramine increases rat brain NA turnover. Conversely, acute and chronic Org 6582 administration yield similar findings, viz. a decrease in turnover. These observations suggest that rat brain 5-HT systems are more resistant than NA systems to adaptive changes following a prolonged inhibition of monoamine uptake.