Homovanillic Acid Levels Research Articles

Neuroprotective effects of swimming training in a mouse model of Parkinson’s disease induced by 6-hydroxydopamine

Parkinson’s disease (PD) is characterized by progressive dopamine (DA) depletion in the striatum. Exercise has been shown to be a promising non-pharmacological approach to reduce the risk of neurodegeneration diseases. This study was designed to investigate the potential neuroprotective effect of swimming training (ST) in a mouse model of PD induced by 6-hydroxydopamine (6-OHDA) in mice. The present study demonstrated that a 4-week ST was effective in attenuating the following impairments resulting from 6-OHDA exposure: (i) depressive-like behavior in the tail suspension test; (ii) increase in the number of falls in the rotarod test; (iii) impairment on long-term memory in the object recognition test; (iv) increase of the reactive species and interleukin 1-beta (IL-1β) levels; (v) inhibition of the glutathione peroxidase (GPx) activity; (vi) rise of the glutathione reductase (GR) and glutathione S-transferase (GST) activities and vii) decrease of DA, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels. The mechanisms involved in this study are the modulation of GPx, GR and GST activities as well as IL-1β level in a PD model induced by 6-OHDA, protecting against the decrease of DA, DOPAC and HVA levels in the striatum of mice. These findings reinforce that one of the effects induced by exercise on neurodegenerative disease, such as PD, is due to antioxidant and anti-inflammatory properties. We suggest that exercise attenuates cognitive and motor declines, depression, oxidative stress, and neuroinflammation induced by 6-OHDA supporting the hypothesis that exercise can be used as a non-pharmacological tool to reduce the symptoms of PD.

Selection for low mortality in laying hens affects catecholamine levels in the arcopallium, a brain area involved in fear and motor regulation

Feather pecking (FP) in laying hens may cause mortality due to cannibalism. Novel breeding methods using survival days of group-housed siblings allow for the genetic selection of laying hens with low mortality (LML: low mortality line) due to cannibalism. Previous studies have demonstrated less fear-related behavior and also less FP in LML hens compared to CL. Selection also caused changes in locomotor behavior in an open field. It is unknown, however, whether selection for low mortality affects central neurotransmitter levels. In this study, brain monoamine levels were measured in the dorsal thalamus, medial striatum, hippocampus and arcopallium of adult laying hens of both LML and CL using HPLC. Brain samples were collected after 5-min of manual restraint. The most prominent line differences were found in the arcopallium. Compared to CL, LML had lower levels of noradrenaline (NA) and 3,4-dihydroxyphenylacetic acid (DOPAC) and tended to have lower levels of dopamine (DA), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). Levels of serotonin (5-HT), 5-HT- and DA-turnover in this brain area were not affected by line. LML showed less fear-related behavior during the restraint than CL. These findings show that selection for low mortality in hens leads to changes of predominantly the dopaminergic system in the chicken's arcopallium, a forebrain somatomotor area also related to fear. This suggests a relationship between catecholamine functioning in this brain area and FP and cannibalistic behavior in chickens and underpins previously found relationships between FP, fear and high activity.

Deep Brain Stimulation Induces Striatal Dopamine Release in Obsessive-Compulsive Disorder

Obsessive-compulsive disorder is a chronic psychiatric disorder related to dysfunctional dopaminergic neurotransmission. Deep brain stimulation (DBS) targeted at the nucleus accumbens (NAc) has recently become an effective treatment for therapy-refractory obsessive-compulsive disorder, but its effect on dopaminergic transmission is unknown. We measured the effects of NAc DBS in 15 patients on the dopamine D2/3 receptor availability in the striatum with [(123)I]iodobenzamide ([(123)I]IBZM) single photon emission computed tomography. We correlated changes in [(123)I]IBZM binding potential (BP) with plasma levels of homovanillic acid (HVA) and clinical symptoms. Acute (1-hour) and chronic (1-year) DBS decreased striatal [(123)I]IBZM BP compared with the nonstimulated condition in the putamen. BP decreases were observed after 1 hour of stimulation, and chronic stimulation was related to concurrent HVA plasma elevations, implying DBS-induced dopamine release. BP decreases in the area directly surrounding the electrodes were significantly correlated with changes in clinical symptoms (45% symptom decrease). NAc DBS induced striatal dopamine release, which was associated with increased HVA plasma levels and improved clinical symptoms, suggesting that DBS may compensate for a defective dopaminergic system.

Interchangeability between 24-hour collection and single spot urines for vanillylmandelic and homovanillic acid levels in the diagnosis of neuroblastoma

The determination of the two urinary catecholamine metabolites homovanillic acid (HVA) and vanillylmandelic acid (VMA) is of crucial importance for the diagnosis and follow-up of neuroblastoma (NB). The standard practice for their measurement requires the use of 24-hour collections that are time consuming and difficult to obtain. In this article, we directly demonstrate that 24-hour collections and single spot urines are interchangeable for the determination of HVA and VMA expressed as ratio on creatinine concentration. This study can be useful for a faster management of NB at onset.

Elevated CSF serotonin and dopamine metabolite levels in overweight subjects

Neurotransmitter systems participate in the regulation of food intake, and their activities are expected to influence eating behavior. We investigated possible associations between body mass index (BMI) and central noradrenaline, serotonin, and dopamine activities, as reflected by the cerebrospinal fluid levels of their main metabolites methoxyhydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA), respectively. We studied 192 subjects (111 males, 81 females) admitted to neurologic clinic for diagnostic investigations that included CSF analysis, and were found not to suffer from any major neurological disease. Subjects were categorized in three groups, namely in lower, in the two middle, and in upper BMI quartiles, the limits calculated separately for males and females. No differences were found in MHPG levels between groups, while subjects in the upper BMI quartile showed significantly elevated levels of 5-HIAA and HVA compared to the levels of subjects in lower and middle quartiles. The results provide evidence that in overweight subjects there are enhanced demands in serotoninergic and dopaminergic signaling for their reward system that may lead to increased motivation for food consumption. The implication of reward centers in eating behavior supports the hypothesis of common mechanisms in obesity and drug addiction.

Neurotoxic effects of berberine on long-term l-DOPA administration in 6-hydroxydopamine-lesioned rat model of Parkinson’s disease

The effects of berberine on long-term administration of L-DOPA in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD) were investigated. Rat models of PD were prepared by 6-OHDA lesions in the ipsilateral sides, and then were treated with berberine (5 and 15 mg/kg) and/or L-DOPA (10 mg/kg) once daily for 21 days. Treatments with either concentration of berberine (5 and 15 mg/kg) in 6-OHDA-lesioned groups decreased the numbers of tyrosine hydroxylase (TH)-immunopositive neurons in the substantia nigra and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum as compared to 6-OHDA-lesioned groups. In addition, dopaminergic neuronal cell death of the ipsilateral sides in 6-OHDA-lesioned groups was attenuated by L-DOPA administration. However, both concentrations of berberine in 6-OHDA-lesioned groups treated with L-DOPA aggravated the numbers of TH-immunopositive neurons in the substantia nigra and the levels of dopamine, norepinephrine, DOPAC and HVA in the striatum as compared to rats not treated with berberine. These results suggest that berberine leads to the degeneration of dopaminergic neuronal cells in the substantia nigra in the rat model of PD with chronic L-DOPA administration. Long-term L-DOPA therapy that may involve possibly neurotoxic isoquinoline agents including berberine should involve monitoring for adverse symptoms.

Homovanillic acid in cerebrospinal fluid of 1388 children with neurological disorders

To determine the prevalence of dopaminergic abnormalities in 1388 children with neurological disorders, and to analyse their clinical, neuroradiological, and electrophysiological characteristics. We studied biogenic amines in 1388 cerebrospinal fluid (CSF) samples from children with neurological disorders (mean age 3y 10mo, SD 4y 5mo; 712 males, 676 females. Correlations among CSF homovanillic acid (HVA) values and other biochemical, clinical, neuroradiological, and electrophysiological parameters were analysed. Twenty-one patients with primary dopaminergic deficiencies were identified. Of the whole sample, 20% showed altered HVA. We report neurological diseases with abnormal CSF HVA values such as pontocerebellar hypoplasia, perinatal asphyxia, central nervous system infections, mitochondrial disorders, and other genetic diseases. Overlapping HVA levels between primary and secondary dopamine deficiencies were observed. Prevalence of low CSF HVA levels was significantly higher in neonatal patients (χ(2) =84.8, p<0.001). Abnormalities in white matter were associated with low CSF HVA (odds ratio 2.3, 95% confidence interval 1.5-3.5). HVA abnormalities are observed in various neurological diseases, but some are probably an unspecific finding. No clear limits for CSF HVA values pointing towards primary diseases can be stated. We report several neurological diseases showing HVA alterations. No neuroimaging traits were associated with low HVA values, except for white matter abnormalities.

Plasma catecholamine metabolite levels and the activities of psychiatric symptoms in systemic lupus erythematosus

Neuropsychiatric systemic lupus erythematosus (NPSLE) is accompanied by neurological or psychiatric symptoms that can be severe. We hypothesized plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) levels were the biological marker that reflected the severity of the NPSLE psychiatric symptoms, and we examined MHPG and HVA levels in systemic lupus erythematosus (SLE) patients. The participants were 42 healthy volunteers and 41 SLE patients. SLE patients were divided into the three groups: NPSLE with psychiatric symptoms (NP group), NPSLE without psychiatric symptoms (NN group), and SLE without neuropsychiatric symptoms (S group). All blood samples were drawn before (T0) and after 4 weeks of treatment (T4) in all SLE patients, and once in the healthy volunteers. Plasma levels of MHPG and HVA were analyzed using high-performance liquid chromatography. Plasma MHPG levels at T0 were significantly increased in the SLE compared to those in healthy volunteers. The NN group had the greatest increase compared with other SLE patient groups. There were no significant differences in plasma HVA levels at T0 between the four groups, and there was also no difference in MHPG and HVA plasma levels between T0 and T4. Hyperactivity of noradrenergic neurons and/or sympathetic nerves might be involved in SLE pathophysiology.

Opsoclonus Associated With Salmonellosis in a 6-Week-Old Infant

A 6-week-old male infant presented with 2 days of fever, emesis, and diarrhea, associated with episodic and chaotic rapid eye movements, determined to be opsoclonus. An electroencephalogram (EEG) obtained during the events was normal. He was treated empirically for meningitis, and an initial workup for neuroblastoma including urine homovanillic acid and vanillylmandelic acid levels, abdominal ultrasonography, and computed tomography (CT) of the chest, abdomen, and pelvis was negative. Stool and blood cultures were positive for Salmonella, and antibiotic regimen was adjusted appropriately. Over the next few days, his fever, emesis, and diarrhea subsided, and the opsoclonus resolved by hospital day 6. He was back to baseline by hospital day 9. Although there have been cases of parainfectious opsoclonus associated with Lyme disease, enterovirus, Streptococcus, and West Nile virus, this represents the first reported pediatric case of opsoclonus associated with salmonellosis. Only 2 such cases in adults have been reported in the literature.

Differential effects of cathinone compounds and MDMA on body temperature in the rat, and pharmacological characterization of mephedrone‐induced hypothermia

Recreational users report that mephedrone has similar psychoactive effects to 3,4-methylenedioxymethamphetamine (MDMA). MDMA induces well-characterized changes in body temperature due to complex monoaminergic effects on central thermoregulation, peripheral blood flow and thermogenesis, but there are little preclinical data on the acute effects of mephedrone or other synthetic cathinones. The acute effects of cathinone, methcathinone and mephedrone on rectal and tail temperature were examined in individually housed rats, with MDMA included for comparison. Rats were killed 2 h post-injection and brain regions were collected for quantification of 5-HT, dopamine and major metabolites. Further studies examined the impact of selected α-adrenoceptor and dopamine receptor antagonists on mephedrone-induced changes in rectal temperature and plasma catecholamines. At normal room temperature, MDMA caused sustained decreases in rectal and tail temperature. Mephedrone caused a transient decrease in rectal temperature, which was enhanced by α(1) -adrenoceptor and dopamine D(1) receptor blockade, and a prolonged decrease in tail temperature. Cathinone and methcathinone caused sustained increases in rectal temperature. MDMA decreased 5-HT and/or 5-hydroxyindoleacetic acid (5-HIAA) content in several brain regions and reduced striatal homovanillic acid (HVA) levels, whereas cathinone and methcathinone increased striatal HVA and 5-HIAA. Cathinone elevated striatal and hypothalamic 5-HT. Mephedrone elevated plasma noradrenaline levels, an effect prevented by α-adrenoceptor and dopamine receptor antagonists. MDMA and cathinones have different effects on thermoregulation, and their acute effects on brain monoamines also differ. These findings suggest that the adverse effects of cathinones in humans cannot be extrapolated from previous observations on MDMA.

Increased melatonin may play dual roles in the striata of a 6-hydroxydopamine model of Parkinson's disease

AimsTo investigate dynamic changes and roles of melatonin (MLT) in the striata of 6-hydroxydopamine (6-OHDA)-treated rats. Main methodsA Parkinson's disease (PD) rat was established by a unilateral injection of 6-OHDA into the right substantia nigra pars compacta (SNc) and the right medial forebrain bundle (MFB) to achieve a complete lesion of the ipsilateral nigrostriatal DA system. Dialysates were collected in the lesioned striatum at different time intervals by in vivo microdialysis. In addition, both contralateral and ipsilateral striatum tissues were collected at two time intervals (10:00 and 22:00h) at 3 and 6weeks after lesioning. The levels of DA, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the dialysates, as well as MLT in the dialysates and tissues were determined using HPLC. Key findingsThe dialysate contents of DA, DOPAC and HVA in the lesioned striatum were significantly decreased (P<0.001) in comparison with those in the controls or in the unlesioned side 3weeks after lesioning while the extracellular level of MLT in the lesioned striatum in these corresponding time intervals distinctly increased when compared with those in the controls (P<0.05). The tissue MLT contents increased in the bilateral striata in different degrees at 6weeks post-lesion (P<0.05). Moreover, increased MLT levels correlate well with rotations or DA changes in the lesioned striatum. SignificanceThese data suggest that 6-OHDA lesion manipulates the MLT secretion pattern. Increased striatal MLT level by a unilateral intracerebral injection of 6-OHDA may play dual roles in the progression of PD in rats.

Schizophrenia: brain morphology and treatment aspects

Since the first findings of enlarged ventricles in computer tomography studies and with the development of MRIbased segmentation, brain morphology findings in schizophrenia point to abnormal structural findings in several brain regions involved in neuronal circuits [1]. One of the often cited environmental risk factors in schizophrenia is cannabis abuse. In an invited review, Malchow et al. [2], however, found inconclusive results with respect to alterations in brain morphology. They assume that chronic cannabis abuse may induce structural changes, whereas in first-episode and high-risk patients, studies need replication. In subjects at high risk and patients with schizophrenia, the gyrification index as a measure of cortico-cortical connection differed from healthy controls in the frontal and parietal cortex [3]. This may be based on the neurodevelopmental abnormalities, since the gyrification pattern is determined during the perinatal period. Accordingly, in a recent postmortem study, a reduced gyrification index has been observed in the parietal cortex in schizophrenia [4] showing no differences between monozygotic twins compared to dizygotic twin pairs which points to the influence of different intrauterine and postnatal factors [5]. Postmortem studies with a resolution on the cellular and even molecular level with, for example, focus on synaptic structural elements [6] may contribute to elucidate the pathophysiology of schizophrenia. Williams et al. [7] investigated neuronal cell density and found decreased pyramidal layer thickness resulting in decreased frontal lobe thickness in schizophrenia patients. They additionally report decreased astrocyte density in the subgenual cingulated cortex and callosal genu for their sample [8], which extends neurobiological hypotheses on the dysfunction of astrocytes in maintaining synaptic stability. Investigations in healthy subjects are indispensable to elucidate risk factors influencing brain volumes and for exclusion of confounding factors such as other diseaserelated and treatment effects. Beside environmental factors, schizophrenia risk genes may contribute to altered brain structures. Trost et al. [9] found a dysbindin-1 gene variant to be associated with hippocampal and prefrontal gray matter volumes. On the molecular level, another risk gene such as brain-derived neurotrophic factor (BDNF) val66met polymorphism has been shown to affect the glutamate system [10]. Moreover, D-amino acid oxidase activator gene (DAOA) variation has been found to affect homovanillic acid levels in cerebrospinal fluid [11]. Unraveling neurobiological effects of such risk factors may contribute to develop a more personalized medicine in psychiatry [12]. Even effects of traditional neuroleptic treatment strategies may be influenced by genetic factors. Giegling et al. [13] found that three haplotype blocks, one among ankyrin repeat and kinase domain containing 1 (ANKK1) and two among dopamine receptor D2 (DRD2) genes, were associated with better clinical improvement in schizophrenia patients. These often are heavy smokers attempting to treat negative and cognitive symptoms themselves. In a clinical trial investigating effects of transdermal nicotine patch, Chen et al. [14], however, found no correlation with replacement doses and only a low smoking cessation rate. They recommend more effective smoking cessation programs for this group of hospitalized patients. Due to restricted therapeutic effects of current treatment strategies in severe psychiatric disorders, the editorial A. Schmitt (&) P. Falkai Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nusbaumstr. 7, 80336 Munich, Germany e-mail: Andrea.Schmitt@med.uni-muenchen.de

Simultaneous Measurement of Serotonin, Dopamine and Their Metabolites in Mouse Brain Extracts by High-Performance Liquid Chromatography with Mass Spectrometry Following Derivatization with Ethyl Chloroformate

In order to measure the levels of serotonin (5-hydroxyltryptamine, 5-HT), dopamine (DA), 3,4-hydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid (HVA) simultaneously, an effective derivatization method followed by high-performance liquid chromatography (HPLC) coupled to electrochemical ionization mass spectrometry was used. The derivatization reaction of biological samples with ethyl chloroformate occurred rapidly at room temperature in aqueous conditions, and the resulting derivatives were isocratically separated with good selectivity using a C18 reversed-phase column within 30 min. The study results showed that the new derivatization procedure offers an excellent means of simultaneous determination of 5-HT, DA and their metabolites in mouse brain homogenates, which are important in a number of physiological and behavioral functions.

Effects of a short-course MDMA binge on dopamine transporter binding and on levels of dopamine and its metabolites in adult male rats

Although the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is often described as a selective serotonergic neurotoxin, some research has challenged this view. The objective of this study was to determine the influence of MDMA on subsequent levels of two different markers of dopaminergic function, the dopamine transporter (DAT) as well as dopamine and its major metabolites. In experiment I, adult male Sprague–Dawley rats were administered either a low or moderate dose MDMA binge (2.5 or 5.0mg/kg×4 with an inter-dose interval of 1h) or saline, and were killed 1 week later. The moderate dose dramatically reduced [3H]WIN 35,428 binding to striatal DAT by 73.7% (P≤0.001). In experiment II, animals were binged with a higher dose of MDMA (10mg/kg×4) to determine the drug's effects on concentrations of serotonin (5-HT), dopamine, and their respective major metabolites 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum and frontal cortex 1 week later. As expected, MDMA significantly reduced 5-HT and 5-HIAA (≥50%) in these structures, while only a marginal decrease in dopamine was noted in the striatum. In contrast, levels of DOPAC (34.3%, P<0.01) and HVA (33.5%, P<0.001) were reduced by MDMA treatment, suggesting a decrease in dopamine turnover. Overall, these findings indicate that while serotonergic markers are particularly vulnerable to MDMA-induced depletion, significant dopaminergic deficits may also occur under some conditions. Importantly, DAT expression may be more vulnerable to perturbation by MDMA than dopamine itself.

Increased Levels of Monoamine-Derived Potential Neurotoxins in Fetal Rat Brain Exposed to Ethanol

Pregnant SD rats were exposed to ethanol (25 % (v/v) ethanol at 1.0, 2.0 or 4.0 g/kg body weight from GD8 to GD20) to assess whether ethanol-derived acetaldehyde could interact with endogenous monoamine to generate tetrahydroisoquinoline or tetrahydro-beta-carboline in the fetuses. The fetal brain concentration of acetaldehyde increased remarkably after ethanol administration (2.6 times, 5.3 times and 7.8 times as compared to saline control in 1.0, 2.0 and 4.0 g/kg ethanol-treated groups, respectively) detected by HPLC with 2,4-dinitrophenylhydrazine derivatization. Compared to control, ethanol exposure induced the formation of 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol, Sal), N-methyl-salsolinol (NMSal) and 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline (6-OH-MTHBC) in fetal rat brains. Determined by HPLC with electrochemical detector, the levels of dopamine and 5-hydroxytryptamine in whole fetal brain were not remarkably altered by ethanol treatment, while the levels of homovanillic acid and 5-hydroxyindole acetic acid in high dose (4.0 g/kg) of ethanol-treated rats were significantly decreased compared to that in the control animals. 4.0 g/kg ethanol administration inhibited the activity of mitochondrial monoamine oxidase (51.3 % as compared to control) and reduced the activity of respiratory chain complex I (61.2 % as compared to control). These results suggested that ethanol-induced alteration of monoamine metabolism and the accumulation of dopamine-derived catechol isoquinolines and 5-hydroxytryptamine-derived tetrahydro-beta-carbolines may play roles in the developmental dysfuction of monoaminergic neuronal systems.

Autoimmune neurological disorders associated with group-A beta-hemolytic streptococcal infection

Although central nervous system (CNS) disorders associated with group-A beta-hemolytic streptococcal (GABHS) infection occur only rarely, Sydenham’s chorea is a well-recognized disease that can arise following infection. Children may develop a tic, obsessive compulsive disorder (OCD), and extrapyramidal movement subsequent to GABHS infection. These disorders have been termed pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). Herein we report one case each of acute disseminated encephalomyelitis (ADEM), PANDAS and subacute encephalitis associated with GABHS infection. To evaluate the pathogenesis of the CNS disorders associated with GABHS infection, we measured levels of neurotransmitters, cytokines, anti-neuronal autoantibodies, and performed immunohistochemistry using patient sera to stain human brain sections. All three cases showed psychiatric behavioral disorders. Immunotherapy was effective, and homovanillic acid levels in the cerebrospinal fluid (CSF) were elevated at the acute stage in all three cases. In each case of ADEM and PANDAS, immunohistochemistry demonstrated neuronal impairment in the basal ganglia during the acute stage. Neuronal immunoreactivity was visualized in the cerebral cortex at the acute stage in the case of subacute encephalitis. There was no direct correlation between immunoreactivity of patient sera on the brain sections and positivity of anti-neuronal autoantibodies or CSF biomarkers. The results suggest that autoimmune responses may modulate neurotransmission, and the use of patient serum for immunohistochemistry is a sensitive screening method for the detection of anti-neuronal autoantibodies in CNS disorders associated with GABHS infection.

Long-term cognitive and neurochemical effects of “bath salt” designer drugs methylone and mephedrone

Introduction/aimsThe use of cathinone-derivative designer drugs methylone and mephedrone has increased rapidly in recent years. Our aim was to investigate the possible long-term effects of these drugs on a range of behavioral tests in mice. Further, we investigated the long-term effects of these drugs on brain neurochemistry in both rats and mice. MethodsWe treated animals with a binge-like regimen of methylone or mephedrone (30mg/kg, twice daily for 4days) and, starting 2weeks later, we performed behavioral tests of memory, anxiety and depression and measured brain levels of dopamine (DA), serotonin (5-HT), their metabolites and norepinephrine (NE). 5-HT and DA transporter (5-HTT and DAT) levels were also measured in rats by [3H]paroxetine and [3H]mazindol binding. ResultsMephedrone reduced working memory performance in the T-maze spontaneous alternation task but did not affect neurotransmitter levels aside from a 22% decrease in striatal homovanillic acid (HVA) levels in mice. Methylone had little effect on behavior or neurotransmitter levels in mice but produced a widespread depletion of 5-HT and 5-HTT levels in rats. ConclusionsBoth methylone and mephedrone appeared to have a long-term effect on either behavioral or biochemical gauges of neurotoxicity in rodents.

Single-Port Laparoscopic Adrenalectomy for Ganglioneuroma: A Case Report

Introduction: Single-port laparoscopy has gained popularity in both the adult and the pediatric populations. Experience thus far is limited in single-port laparoscopy for adrenalectomy. We present a 4-minute video of a single-port laparoscopic adrenalectomy performed for benign disease in a girl. Methods: The patient was a 16-year-old girl (49 kg) who was found to have an incidental 3.2-cm calcified mass in the right adrenal gland. The patient was normotensive and clinically asymptomatic. Urine metanephrines, Vanillylmandelic acid (VMA), Homovanillic acid (HVA), norepinephrine, epinephrine, and dopamine levels were normal. At the time of surgery, the patient was placed in a lateral decubitus position with the right flank elevated. A 2-cm transverse, muscle-splitting incision was made in the flank at the mid-axillary line, and the TriPortTM (Advanced Surgical Concepts, Wicklow, Ireland) was placed into the peritoneum. A 5-mm, 30-degree endoscope and two 5-mm straight-working instruments were used for dissection. A 5-mm self-retaining retractor was used to retract the liver. The medial aspect of the gland was dissected from the inferior vena cava to expose the main adrenal pedicle. The main adrenal pedicle was ligated with 5-mm titanium clips and divided. Dissection continued superiorly, where the superior adrenal vein was clipped and divided. The inferior aspect of the adrenal gland was freed from the superior aspect of the kidney, and the inferior adrenal pedicle was clipped and divided. The adrenal gland was removed intact. Results: The operative time was 124 minutes with minimal blood loss. The patient began a liquid diet the night of surgery. She was discharged to home on the third postoperative day. The pathology revealed mature ganglioneuroma. At her 6-month follow-up visit, the results of renal ultrasonography and urinary catecholamines remained normal. Conclusion: Since the initial description in the adult literature in 1992,1 laparoscopic adrenalectomy has become the accepted approach for children with benign disease.2 The identification of incidental adrenal lesions is increasing in the pediatric population, and resection is recommended because malignancy may be found in up to 30%.3 The flank approach allowed for direct access to the retroperitoneum. As experience increases, the single-port laparoscopic approach through the umbilicus can provide a virtually scarless operation. This group of patients may be excellent candidates for a single-port laparoscopic approach to adrenalectomy. No competing financial interests exist. Runtime of video: 4 mins Presented at the International Pediatric Endosurgery Group's 20th Annual Congress of Endosurgery in Children, May 3–7, 2011, Prague, Czech Republic.

Effects of Echinacoside on Histio-central Levels of Active Mass in Middle Cerebral Artery Occlusion Rats

ObjectiveTo investigate the effects of echinacoside on the extracellular striatal levels of norepinephrine (NE), dopamine (DA), homovanillic acid (HVA), 3, 4-dihydroxyphenylethanoid acid (DOPAC), 5-hydroxyindoleacetic acid (HIAA), and 5-hydroxytryptamine(5-HT) in middle cerebral artery occlusion (MCAO rats. MethodsThe middle cerebral artery was occluded in male Sprague-Dawley rats. Three days later microdialysis probes were placed into the right striatum of MCAO rat brains and the brains were perfused with Ringer's solution at a rate of 1.5 µL/min. Cerebral microdialysates were collected every 30 minutes from awake and freely moving rats before assaying for NE, DA, HVA, DOPAC, HIAA, and 5-HT levels by reverse phase HPLC with electrochemistry. ResultsThree days after MCAO, the extracellular striatal levels of NE, DA, DOPAC, HIAA, HVA, and 5-HT of the MCAO rats increased significantly (at least P<0.05 vs. control). However, simultaneous treatment with echinacoside (30.0 or 15.0 mg/kg) attenuated these increases (at least P<0.05 vs. non-treated model rats). ConclusionThese results imply that echinacoside may protect striatal dopa minergic neurons from the injury induced by MCAO and may help prevent and treat cerebral ischemic diseases.

Effect of switching to risperidone after unsuccessful treatment with aripiprazole on plasma monoamine metabolites level in the treatment of acute schizophrenia

In the treatment of acute schizophrenia, risperidone and aripiprazole are both placed the first line antipsychotics. These two antipsychotics have different pharmacological effects. We investigated the effects of risperidone on plasma levels of homovanillic acid (HVA) and 3-methoxy-4hydroxyphenylglycol after unsuccessful aripiprazole treatment in acute schizophrenia. Ten Japanese patients with acute schizophrenia were enrolled to this study. Plasma levels of monoamine metabolites were analyzed with high-performance liquid chromatography with electrochemical detection. Risperidone improved the symptoms and 4 of 10 patients were responders. Risperidone showed a tendency to decrease plasma HVA (pHVA) levels in responders (p = 0.068), but not in non-responders (p = 1.0). At baseline, pHVA levels of responders were significantly higher than that of non-responders (p = 0.033). A trend for negative correlation was found between pHVA at baseline and the changes in Positive and Negative Syndrome Scale-Total (p = 0.061, r = -0.61). Our results suggest that high pHVA level before switching may predict good response to the second line antipsychotics after unsuccessful first antipsychotic treatment. If aripiprazole is not effective in acute schizophrenia, switching to risperidone may be effective and reasonable strategy for improving symptoms.