Antioxidant and Anti-Stress Effects of Taurine Against Electric Foot-Shock-Induced Acute Stress in Rats.

In the present study, we evaluated the antioxidant and anti-stress activities of taurine in electric foot-shock stress model rats. Taurine supplementation markedly increased the hepatic glutathione (GSH) levels, compared to the levels in the stress group. In addition, activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were improved in the taurine-treated group. Plasma cortisol and dehydroepiandrosterone-sulfate (DHEA-S) levels were significantly reduced in the taurine-supplemented group compared to those in the stress group. In contrast, the levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were markedly increased in the taurine or betaine-treated group compared to those in the stress group. It may be concluded that taurine produces beneficial effects in the form of antioxidant status and biochemical alterations in foot-shock-induced acute stress in rats.

Not only serotonergic system, but also dopaminergic system involved in albiflorin against chronic unpredictable mild stress-induced depression-like behavior in rats.

Albiflorin (AF), separated from the root of Paeonia lactiflora Pall, possesses neuro-protective and anti-inflammatory activities. Based on previous results, our present research aims to investigate the antidepressant-like activity of AF in chronic unpredictable mild stress (CUMS)-induced rat model of depression. Eight weeks of CUMS process successfully established depression-like rat model, as evidenced by the enhanced immobility time in forced swimming test and the reduced sucrose preference, which were reversed to near normal by AF (20 mg/kg and 40 mg/kg) and fluoxetine (3 mg/kg; positive drug) treated. Compared to non-treated depression-like rats, the increased levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HTAA) in serum and hypothalamus, and the reduced expressions of 5-HT1A receptor and 5-HT2A receptor in hypothalamus were observed after AF and fluoxetine oral administration indicating that AF-mediated antidepressant-like effect may be related to the normalization of serotonergic system. Additionally, four-week AF treated rats significantly showed improvement in the reduced dopamine and noradrenalin concentration in serum and hypothalamus as observed on depression-like rats. Altered levels of tyrosine hydroxylase, dopamine D2 receptor and dopamine transporter in hypothalamus reverted to the normal level after treatment with both AF and fluoxetine. All these data demonstrate that not only serotonergic system, but also dopaminergic system is involved in AF-mediated antidepressant-like effect in CUMS-induced rat model of depression.

Effects of Chinese herbal medicine Ningdong granule on regulating dopamine (DA)/serotonin (5-TH) and gamma-amino butyric acid (GABA) in patients with Tourette syndrome.

Many studies have indicated that a variety of neurotransmitters are implicated in the pathophysiology of Tourette syndrome (TS), including dopamine (DA), serotonin (5-TH), homovanillic acid (HVA), and gamma-amino butyric acid (GABA). Our previous studies found that Ningdong granule (NDG) is effective on a rat model with TS. NDG can regulate the metabolic disturbance of DA, 5-TH and HVA in the rat brain. However, the mechanisms of NDG in patients with TS are still not clear. To further evaluate the efficiency, safety, and possible mechanisms of NDG, a randomized and double-blind study was carried out. One hundred and twenty patients with TS were enrolled in this study, that were randomly divided into 4 groups (NDG group, Haloperidol (Hal) group, NDG + Hal group and Control group). First, the efficiency of NDG was assessed using the Yale Global Tic Severity Score (YGTSS). Second, the concentration of DA, HVA, 5-TH, 5-hydroxyindoleacetic acid (5-HIAA) and GABA in sera were tested by ELISA. In addition, the influence of NDG on liver and renal function was recorded. We found that NDG could ameliorate tics significantly according the YGTSS score. The concentration of HVA and GABA were increased after treatment with NDG. Furthermore, we found that there was no liver or renal damage in children treated with NDG. We also found that the NDG + Hal group was more effective and safe compared with other groups. In conclusion, the current study indicates that NDG might be effective on patients with TS by regulating dopamine (DA)/serotonin (5-TH) and gamma-amino butyric acid (GABA).

[Influence of iridoid from Valeriana jatamansi on 5-HT and 5-HIAA in rats with irritable bowel syndrome].

OBJECTIVE: To investigate the mechanism of iridoid from Valeriana jatamansi treating irritable bowel syndrome. METHOD: Sixty male SD rats were equally divided into 6 groups (2 controls, 1 model and 3 treatment doses) with 10 rats per group. The test groups were administered with iridoid (24.92, 12.46, 6. 23 mg x kg(-1)) while the control groups were administered with fluoxetine (2.5 mg x kg(-1), positive control) or distilled water (negative control). The model was established by chronic stress and independent feeding. The influence of iridoid from V. jatamansi on 5-HT and 5-HIAA in colon, serum and hypothalamic were observed in all groups. RESULT: In the model group, the content of 5-HT in colon and serum increased significantly, but the content of 5-HT in hypothalamic decreased significantly. The content of 5-HIAA and the value of 5-HT/5-HIAA had no significant change. In three iridoid-treated groups, the content of 5-HT in colon and serum decreased, but the content of 5-HT in hypothalamic increased. The content of 5-HIAA had no significant change. The value of 5-HT/5-HIAA in colon and serum reduced. CONCLUSION: The mechanism of iridoid from V. jatamansi treating irritable bowel syndrome may be related to the regulation effect to the levels of 5-HT from Gastrointestinal to central nervous system.

Effect and mechanism of senkyunolide I as an anti-migraine compound from Ligusticum chuanxiong.

OBJECTIVE: To evaluate the analgesic and anti-migraine activities of senkyunolide I from Ligusticum chuanxiong. METHODS: Mice were orally administered various doses of senkyunolide I, and their pain levels were assessed in a hot-plate test and by application of acetic acid. The levels of 5-hydroxytryptamine (5-HT), 5-hydroxytryptophan (5-HTP), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE) and dopamine (DA) in plasma and brain were assessed, and the monoamine turnover rates (5-HT/5-HTP, 5-HIAA/5-HT and NE/DA) were also calculated. RESULTS: Mice given senkyunolide I at 16 and 32 mg/kg had significantly elevated pain thresholds in the hot-plate test, and a dose of 32 mg/kg also reduced the number of abdominal writhing responses caused by acetic acid. Significant improvements were observed in the neurotransmitter levels of the drug-treated rats compared with the saline-administered controls. Compared to the rats with nitroglycerin-induced migraines, the levels of nitric oxide in the plasma and whole brain of rats given senkyunolide I were lower. CONCLUSIONS: The present study suggests that senkyunolide I may be an active component of L. chuanxiong, traditionally used to treat migraine. The mechanism of pain relief in migraine model rats may be through adjusting the levels of monoamine neurotransmitters and their turnover rates, as well as decreasing nitric oxide levels in the blood and brain. Therefore, senkyunolide I may be developed as a potential treatment for migraine pain.

Downregulated hypothalamic 5-HT3 receptor expression and enhanced 5-HT3 receptor antagonist-mediated improvement in fatigue-like behaviour in cholestatic rats.

The serotonin neurotransmitter system, including the 5-HT(3) receptor, has been implicated in the genesis of fatigue in patients with liver disease. Therefore, we examined the possible role of 5-HT(3) receptors in cholestasis-associated fatigue. Rats were either bile duct resected (BDR) or sham resected and studied 10 days postsurgery. A significant decrease in hypothalamic 5-HT(3) receptor expression was detected by immunohistochemistry and Western blot in BDR vs sham rats, coupled with increased hypothalamic serotonin turnover identified by an elevated 5-hydroxyindoleacetic acid (5-HIAA) to 5-HT ratio in BDR vs sham rats. To examine fatigue-like behaviour, an activity meter was used. BDR rats exhibited significantly lower locomotor activity than did sham animals. Subcutaneous injection of the 5-HT(3) receptor antagonist tropisetron (0.1 mg kg(-1)) resulted in significantly increased locomotor activity in BDR rats compared to the activity in saline-treated controls, but was without effect in sham rats. However, a 10-fold higher dose of tropisetron significantly increased locomotor activity in both BDR and sham rats compared to saline-injected controls. These findings indicate that cholestasis in the rat is associated with increased hypothalamic serotonin turnover, decreased hypothalamic 5-HT(3) receptor expression, and enhanced sensitivity to locomotor activation induced by 5-HT(3) receptor antagonism, thereby implicating the 5-HT(3) receptor system in cholestasis associated fatigue.

Antidepressant-like effects of the mixture of honokiol and magnolol from the barks of Magnolia officinalis in stressed rodents.

Honokiol and magnolol are the main constituents simultaneously identified in the barks of Magnolia officinalis, which have been used in traditional Chinese medicine to treat a variety of mental disorders including depression. In the present study, we reported on the antidepressant-like effects of oral administration of the mixture of honokiol and magnolol in well-validated models of depression in rodents: forced swimming test (FST), tail suspension test (TST) and chronic mild stress (CMS) model. The mixture of honokiol and magnolol significantly decreased immobility time in the mouse FST and TST, and reversed CMS-induced reduction in sucrose consumption to prevent anhedonia in rats. However, this mixture was unable to affect ambulatory or rearing behavior in the mouse open-field test. CMS induced alterations in 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) levels in various brain regions of rats. An increase in serum corticosterone concentrations and a reduction in platelet adenylyl cyclase (AC) activity were simultaneously found in the CMS rats. The mixture of honokiol and magnolol at 20 and 40 mg/kg significantly attenuated CMS-induced decreases of 5-HT levels in frontal cortex, hippocampus, striatum, hypothalamus and nucleus accumbens. And it markedly increased 5-HIAA levels in frontal cortex, striatum and nucleus accumbens at 40 mg/kg and in frontal cortex at 20 mg/kg in the CMS rats. A subsequent reduction in 5-HIAA/5-HT ratio was found in hippocampus and nucleus accumbens in the CMS rats receiving this mixture. Furthermore, the mixture of honokiol and magnolol reduced elevated corticosterone concentrations in serum to normalize the hypothalamic-pituitary-adrenal (HPA) hyperactivity in the CMS rats. It also reversed CMS-induced reduction in platelet AC activity, via upregulating the cyclic adenosine monophosphate (cAMP) pathway. These results suggested that the mixture of honokiol and magnolol possessed potent antidepressant-like properties in behaviors involved in normalization of biochemical abnormalities in brain 5-HT and 5-HIAA, serum corticosterone levels and platelet AC activity in the CMS rats. Our findings could provide a basis for examining directly the interaction of the serotonergic system, the HPA axis and AC-cAMP pathway underlying the link between depression and treatment with the mixture of honokiol and magnolol.

Role of osteopathic manipulative treatment in altering pain biomarkers: a pilot study.

CONTEXT: Underlying mechanisms explaining the effects of osteopathic manipulative treatment (OMT) are poorly defined. The authors evaluate various nociceptive (pain) biomarkers that have been suggested as important mediators in this process. OBJECTIVE: To determine if OMT influences levels of circulatory pain biomarkers. METHODS: In a prospective, blinded assessment, blood was collected from 20 subjects (10 with chronic low back pain [LBP], 10 controls without chronic LBP) for 5 consecutive days. On day 4, OMT was administered to subjects 1 hour before blood collection. Blood was analyzed for levels of beta-endorphin (betaE), serotonin (5-hydroxytryptamine [5-HT]), 5-hydroxyindoleacetic acid (5-HIAA), anandamide (arachidonoylethanolamide [AEA]), and N-palmitoylethanolamide (PEA). A daily questionnaire was used to monitor confounding factors, including pain and stress levels, sleep patterns, and substance use. RESULTS: Increases from baseline in betaE and PEA levels and a decrease in AEA levels occurred immediately posttreatment. At 24 hours posttreatment, similar biomarker changes from baseline were observed. A decrease in stress occurred from baseline to day 5. The change in PEA from baseline to 24 hours posttreatment correlated with the corresponding changes in stress. Subgroup analysis showed that subjects with chronic LBP had significantly reduced 5-HIAA levels at 30 minutes posttreatment (P=.05) and 5-HT levels at 24 hours posttreatment (P=.02) when compared with baseline concentrations. The increase in PEA in subjects with chronic LBP at 30 minutes posttreatment was two times greater than the increase in control subjects. CONCLUSION: Concentrations of several circulatory pain biomarkers were altered after OMT. The degree and duration of these changes were greater in subjects with chronic LBP than in control subjects without the disorder.

[Therapeutic effect of acupuncture on female's climacteric depression and its effects on DA, NE and 5-HIAA contents].

OBJECTIVE: To observe therapeutic effects of acupuncture on female's climacteric depression and to study on the mechanism. Methods Sixty cases enrolled were randomly divided into an acupuncture group and a control group, 30 cases in each group. In the acupuncture group, acupuncture were given at Ganshu (BL 18), Shenshu (BL 23), Xinshu (BL 15), etc. with uniform reinforcing-reducing method, once each day, and the control group were treated with oral administration of fluexertine hydrochloride, 20 mg, once daily. HAMD scale was used for assessment before treatment and 2,4,6 weeks after treatment. Blood dopamine (DA), norepinephrine (NE) and 5-hydroxy-indoleacetic acid (5-HIAA) contents were detected before treatment and after one therapeutic course. Results The total effective rate was 86.7% in the acupuncture group and 92.9% in the control group with no significant difference between the two groups (P > 0.05). After treatment, DA content increased significantly in the acupuncture group with a significant difference as compared with that of the control group (P < 0.05); and after treatment NE and 5-HIAA contents in the two groups significantly increased as compared with that before treatment (P < 0.05, P < 0.01), with no significant difference between the two groups (P > 0.05). Conclusion Acupuncture can benignly and comprehensively regulate general functions, and increase contents of monoamines in the body, so as to play the role of anti-depression.

Natural killer cells and lymphocytes increase in women with breast cancer following massage therapy.

Women diagnosed with breast cancer received massage therapy or practiced progressive muscle relaxation (PMR) for 30-min sessions 3 times a week for 5 weeks or received standard treatment. The massage therapy and relaxation groups reported less depressed mood, anxiety, and pain immediately after their first and last sessions. By the end of the study, however, only the massage therapy group reported being less depressed and less angry and having more vigor. Dopamine levels, Natural Killer cells, and lymphocytes also increased from the first to the last day of the study for the massage therapy group. These findings highlight the benefit of these complementary therapies, most particularly massage therapy, for women with breast cancer.

Repetitive transcranial magnetic stimulation (rTMS) at high and low frequency: an efficacious therapy for major drug-resistant depression?

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is proposed for the treatment of drug-resistant depression. Studies performed in accordance with evidence-based medicine (EBM) are scarce, particularly in seeking optimal treatment and evaluation parameters. We aimed to test various types of rTMS in a large sample of depressed patients following EBM rules and to investigate treatment-related changes in plasma levels of neurotransmitters involved in depression. METHODS: Seventy-one drug-resistant depressed patients were randomly assigned to low (1 Hz) or high (17 Hz) rate TMS, applied for 5 days over the left dorsolateral prefrontal cortex (L-DLPFC). Patients were separated into two study designs. One group (20 patients) received only active treatment, while the other entered a double-blind, placebo-controlled, crossover design. Pre- and post-treatment blood samples were taken for evaluation of plasma levels of dopamine and serotonin. RESULTS: After a week of treatment patients had a measurable benefit. However, overall the placebo stimulation did not differ significantly from real stimulation, nor were differences observed between the two rates of rTMS. The only difference emerged when the real stimulation was applied at 17 Hz following placebo treatment. Plasma levels of neurotransmitters between active and placebo rTMS were similar. CONCLUSIONS: Using the treatment schedule of 1 week, although a clinical improvement after active treatment was indeed observed, this was both clinically and biochemically indistinguishable from that seen in the placebo arm. SIGNIFICANCE: This suggests that most of the previous emphasis, for short period of treatment, should be tempered down and that further work is required in order to verify whether optimal stimulation and evaluation parameters for TMS-treatment of depression beyond the placebo effect may be found following EBM rules.

Role of omega-3 fatty acids as a treatment for depression in the perinatal period.

OBJECTIVES: To consider the possible rationale and utility of omega-3 fatty acids as a treatment for depression in the perinatal period. METHOD: A review of published and unpublished research was undertaken, using electronic databases, conferences proceedings and expert informants. RESULTS: Relevant bodies of evidence include an epidemiological link between low fish intake and depression. Laboratory studies show correlations between low omega-3 fatty acid levels and depression, as well as reduced levels of omega-3 in non-depressed women during the perinatal period. Treatment studies using omega-3 in patients with mood disorders further support an omega-3 contribution, as do neuroscientific theories. Research into omega-3 and infant development also highlights potential effects of depletion in the perinatal period and supports infant safety and benefits of supplementation. CONCLUSIONS: There is a relative lack of knowledge about the safety of standard antidepressants in the perinatal period. There is a clear need for more research into alternative treatments, such as omega-3 fatty acids, in the management of depression in the perinatal period.

Serotonin, serotonin 5-HT(1A) receptors and dopamine in blood peripheral lymphocytes of major depression patients.

There are increasing evidences of cell markers present in the immune and the nervous systems. These include neurotransmitter receptors and transporters. Serotonin receptor subtypes are related to depression and also have been shown to be present in certain cells of the immune system. In the present report, we determined the presence of 5-HT(1A) receptors by the binding of the selective agonist 8-hydroxy-2-(di-n-propyl-amino)tetralin in lymphocytes of peripheral blood isolated by Ficoll/Hypaque gradients from controls and depressed patients. The capacity of these receptors was around 24 fmol/10(6) cells in both groups of subjects, without significant difference among them. The affinity was in the nM range and either differ between controls and patients. Serotonin, 5-hydroxyindoleacetic acid, dopamine and 3,4-dihydroxyphenylacetic acid were determined by HPLC with electrochemical detector. There were no significant differences between controls and major depression patients in the values obtained for rich and poor platelet plasma or in the isolated cells. However, there was a reduction in serotonin turnover rate indicated by an increase in the ratio serotonin/5-hydroxyindoleacetic acid, but not in that of dopamine, in lymphocytes of major depression patients. Thus, there is a serotonergic dysfunction in immune circulating cells of major depression patients, without changes in the number of 5-HT(1A) receptors, although the coupling of these receptors to transduction mechanisms could be affected and may be related to the alteration of 5-HT turnover rate.

[An experimental study of the effect of Zofran on the manifestations of a primary reaction to irradiation]. / Eksperimental'noe issledovanie vliianiia zofrana na proiavleniia pervichnoi reaktsii na obluchenie.

Zofran is a selective antagonist of 5-HT3 receptors which effectively prevents postradiation dyspeptic and behavioral disorders in dogs and rats. Administration of the drug normalizes intestinal absorption and propulsion activity in irradiated animals.

Simultaneous brain and blood microdialysis study with a new removable venous probe. Serotonin and 5-hydroxyindolacetic acid changes after D-norfenfluramine or fluoxetine.

A removable intravenous microdialysis probe was developed and simultaneously used with a removable microdialysis probe placed in the lateral hypothalamus (LH). Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) changes in blood and brain dialysates were measured by HPLC-EC after an i.p. injection of 5 mg/kg d-norfenfluramine (dNF) or 10 mg/kg fluoxetine (FLU) in freely moving rats. 5-HT in the LH significantly increased after both drugs, but the rise was larger and faster with dNF [F(7,28)=4.0 p<0.05] than with FLU [F(5,20)=5.0 p<0.01]. By contrast, in venous blood 5-HT increased after FLU [F(5,20)=2.96 p<0.05] but not after dNF. 5-HIAA after both drugs continued decreasing significantly in the LH [dNF F(7,28)=11.4 p<0.01; FLU F(5,20)=22.8 p<0.01], but it did not change in blood. Simultaneous dialysis in brain and blood allowed evaluation of the differential effects of dNF and FLU on 5-HT and 5-HIAA in the two places. Removable venous probes prevented the inflammatory reaction that may occur around permanently implanted probes, and the dialysis could be more efficient and with less risk of clogging.

The effect of discontinuing dehydroepiandrosterone supplementation on Zucker rat food intake and hypothalamic neurotransmitters.

OBJECTIVE: Dehydroepiandrosterone (DHEA) decreases body weight and food intake of the obese Zucker rat, a model of youth-onset obesity associated with hyperphagia. The effects of discontinuing DHEA treatment on these parameters, however, has not been investigated. This question was studied in rats that had been maintained on DHEA-supplemented (0.0%, 0.06%, 0.15%, 0.3% or 0.6%) diets for 7 days. METHOD: The results were correlated with regional levels of hypothalamic neurotransmitters in rats treated with 0.6% DHEA for 7 days in a separate experiment. Neurotransmitter changes were evaluated after Day 0 (7 days of treatment), and Day +1 and Day+2 post-DHEA. RESULTS: Upon removing dietary DHEA, rats immediately (+1 day) consumed significantly more food than while on the DHEA-supplemented diet. Indeed, they consumed even more food than the group that had always been on the DHEA-free diet. This intake above control lasted for as long as +9 days post-DHEA treatment. After 7 days of DHEA treatment, lateral hypothalamic (LH) serotonin (5-HT) and dopamine (Dpm) were elevated significantly (P < 0.05) immediate changes in 5-HT and Dpm returned to baseline by day 2 of post-DHEA treatment. No significant changes occurred in either the ventromedial hypothalamus (VMH) or the paraventricular nucleus (PVN). CONCLUSIONS: These observations suggest that there is a possible relationship between increases of LH 5-HT and Dpm with 0.6% DHEA treatment. Both are inhibitory to food intake and DHEA at the 0.6% dose causes hypophagia after 7 days of treatment (i.e. 0 days). Subsequent decreases of these monoamines occurred during the post-DHEA period at both +1 and +2 days. Return of these inhibitory monoamines to baseline could be responsible for reversal of the hypophagia, however, they do not rule out the production of a separate stimulator of food intake.

Aspartame, behavior, and cognitive function in children with attention deficit disorder.

OBJECTIVE: To determine the effects of large doses of aspartame on behavior, cognition, and monoamine metabolism in children with attention deficit disorder. DESIGN: A randomized, double-blind, placebo-controlled crossover study of unmedicated children meeting Diagnostic and Statistical Manual of Mental Disorders (3rd ed) criteria for attention deficit disorder. SETTING: Behavioral assessments were performed in the child's home by their parents and in the classroom by a teacher. Cognitive tests were administered and blood drawing was performed during a 2-day inpatient admission to our Children's Study Center. INTERVENTIONS: Administration of aspartame (single morning dose, 34 mg/kg) or placebo for alternate 2-week periods. MAIN OUTCOME MEASURES: Behavioral and cognitive tests included the Matching Familiar Figures Test (MFFT), Children's Checking Task (CCT), the Airplane Test, the Wisconsin Card Sorting Test (WCST), the Subjects Treatment Emergent Symptom Scale (STESS), the Multigrade Inventory for Teachers (MIT), and the Conners Behavior Rating Scale. Blood was drawn for complete blood cell count and liver function tests, as well as amino acid, methanol, formate, serotonin, and monoamine metabolite analyses, and urine was collected for measurement of catecholamine and monoamine metabolite excretion. RESULTS: No clinically significant differences between aspartame and placebo were found for the STESS, MIT, or Conners ratings, or for the MFFT, CCT, WCST, or Airplane cognition tests. Also, no differences were noted for any of the biochemical measures, except for the expected increase in plasma phenylalanine and tyrosine following aspartame. CONCLUSIONS: The findings indicate that aspartame at greater than 10 times usual consumption has no effect on the cognitive and behavioral status of children with attention deficit disorder. In addition, aspartame does not appear to affect urinary excretion rates of monoamines and metabolites.

Effect of dehydroepiandrosterone on neurotransmitter levels and appetite regulation of the obese Zucker rat. The Obesity Research Program.

The obese Zucker rat is a model of youth-onset obesity associated with hyperphagia. In this study, dehydroepiandrosterone's effect at decreasing food intake and body weight in the obese Zucker rat was investigated. Rats were treated with a dehydroepiandrosterone-supplemented diet (0.0, 0.06, 0.15, 0.3, or 0.6%) for 7 days. The 0.3 and 0.6% treatment groups showed a dramatic decrease in daily food intake, which was evident the 1st day. In addition to the reduction in food intake, body weight changes also were affected significantly in the high-dose treatment groups. The possibility that these dehydroepiandrosterone-induced changes were correlated to perturbations in central neurotransmitter levels associated with appetite control was investigated. The hypothalamus, frontal cortex, striatum, and hippocampus of dehydroepiandrosterone-treated animals were assayed for neurotransmitters known to have inhibitory or stimulatory effects on feeding behavior (serotonin, dopamine, norepinephrine, and epinephrine). Significant differences from steroid-free controls were noted only in the levels of hypothalamic serotonin in animals treated with dehydroepiandrosterone. Serotonin in the hypothalamus has been shown to decrease feeding behavior. The magnitude of dehydroepiandrosterone's effect on hypothalamic serotonin correlated with its effect on feeding behavior. Thus, dehydroepiandrosterone may reduce hyperphagia by altering hypothalamic levels of serotonin.

Effects of estradiol on brain aminergic turnover of the female rainbow trout (Oncorhynchus mykiss) at the beginning of vitellogenesis.

Brain serotonin and dopamine (DA) turnovers in the female rainbow trout were studied at the beginning of the vitellogenesis and related to blood estradiol (E2) levels; pituitary and plasma gonadotropin (GtH) were also assayed. Ovariectomy did not modify brain aminergic turnover. E2 replacement on ovariectomized fish increased hypothalamic DA turnover (increased DA and increased DA metabolites). E2 stimulated GtH synthesis (positive feedback) but did not enhance GtH release; hypothalamic E2-mediated aminergic inhibition upon release was suspected. Individual relations between blood E2 levels and catecholaminergic neurotransmitters were determined. A linear positive correlation (r = 0.82) was found for the hypothalamus, but not for the pituitary, the preoptic area, or the telencephalon. These data suggest that an activation of hypothalamic tyrosine hydroxylase (the limiting step of catecholamines synthesis) by E2 could develop as vitellogenesis proceeds.

Biochemistry of migraine.

The biochemistry of migraine is complex. Many contradictory or never replicated findings in often small patient groups have been published. The following observations in the platelet-free plasma and urine appear to have some solid basis and will be discussed: 1) systemic derangement of 5-HT metabolism, relevant to the peripheral vascular component of migraine pathophysiology, 2) changes in neuroexcitatory amino acids and magnesium, which may reflect a predisposition of the migraine patient, notably those having attacks with aura, to develop spreading depression, 3) alterations in methionine-enkephalin levels, which may be a useful marker to discriminate between tension headache and migraine, 4) hormonal fluctuations which seem important to set the threshold for an attack, 5) changes of vasoactive peptides in the cranio-vascular circulation, providing the first human evidence that the trigemino-vascular system indeed is relevant in migraine, and 6) catecholaminergic changes suggesting sympathetic overactivity. Finally distinct biochemical differences between patients with migraine without aura and patients with tension headache on one hand, and between patients with migraine with aura and patients with migraine without aura on the other hand will be emphasized. Findings in platelets will be discussed only if they are complementary and supportive to the plasma and urine data.