Olfactory bulbus volume and olfactory sulcus depth in migraine patients: an MRI evaluation.

OBJECTIVES: To compare the measurements of olfactory bulb volume and olfactory sulcus depth in patients with migraine and a control group. METHODS: The study included the cranial MRI (1.5 T) images of 200 adults diagnosed with migraine and a control group of 100 subjects without migraine. The control group mainly consisted of the patients with non-migraneous headache. The measurements were obtained from coronal T2-weighted images for standard olfactory bulb (OB) volume and olfactory sulcus (OS) depth. RESULTS: The OB volume and OS depth values were lower in the migraine group than in the control group. In the migraine group, left OB volume of the males was significantly lower than those of the females. In both the migraine and control groups separately, the left-side OB volume values and the right side OS depth values were significantly greater than those of the contralateral side. There were positive correlations between right and left OB volume, and right and left OS depth values. No change was seen in OB volume and OS depth values according to gender. In older patients, a decrease was determined in the right and left OB volume, and the left-side OS depth values. There was a negative correlation between osmophobia and OB volume values. In migraine patients with osmophobia, the OB volume values were significantly decreased. CONCLUSION: OB volume values were lower in migraine patients. When osmophobia was present, the OB volume was lower than that of the non-osmophobia migraine patients. Olfactory function monitoring with olfactory tests and olfactory volume monitoring on MRI can be recommended for all migraine patients to diagnose olfactory dysfunction earlier, especially those with osmophobia. Because their OB volume values were detected as lower than those of the migraine patients without osmophobia, it may be thought that blood flow changes and osmophobia may affect the olfactory bulb volume shrinkage in migraine patients.

Validation of the Comprehensive ICF Core Set for Multiple Sclerosis: A Turkish clinical perspective.

Objectives: The aim of this study was to evaluate the results of the construct validity of the Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for Multiple Sclerosis (MS) and to identify the impact of MS on specific health domains according to the ICF categories in Turkish individuals. Patients and methods: Between December 2011 and December 2012, a total of 150 individuals with MS (69 males, 81 females; mean age: 39.8±8.0 years; range, 19 to 52 years) who were diagnosed by a neurologist at least six months previously were included. The Comprehensive ICF Core Set for MS was used to assess functioning, disability, and environmental factors in all participants. The Spearman correlation coefficient was used to determine construct validity of the ICF Core Set between the ICF components and disease-specific and general measurements. Results: The most frequently coded impairments in the body functions component were b280 sensation of pain, b134 sleep functions, b1301 motivations, and b740 muscle endurance functions. The most frequently coded impairments in the body structures component were s110 structure of brain, s120 spinal cord and related structures and s750 structure of lower extremity. A significant problem was documented in 47 of the 53 categories of the activities and participation. Of the 38 categories in the environmental factors, 23 were identified as a facilitator, while 12 categories were identified as a barrier. All body function, structure, activities and participation and environmental factors categories showed a significant correlation with disease-specific and generic measures. Conclusion: Based on these results, the ICF Core Set may help to determine major facilitators or barriers to functioning and disability and a targeted rehabilitation approach in patients with MS.

Evaluation of putamen area and cerebral peduncle with surrounding cistern in patients with Parkinson's disease: is there a difference from controls in cranial MRI?

OBJECTIVES: Nigrostriatal dopaminergic neuron loss is essential in pathogenesis of Parkinson's disease (PD). The purpose of this study was to evaluate nigrostriatal structures including the putamen, cerebral peduncle, widths of interpeduncular cistern, and ambient cistern around the midbrain with conventional cranial magnetic resonance images (MRI) in patients with PD. METHODS: The MRI of 56 subjects was included, which was selected from the radiological data system for this retrospective study. The 29 patients with idiopathic PD were included and their disease duration, Hoehn&Yahr stage, and Levodopa equivalent dose (LED) were recorded. The 27 controls had a normal neurologic examination and cranial MRI. All subjects in the patient and control groups had right-hand dominance. Putamen and cerebral peduncle areas and widths of interpeduncular and ambient cisterns were measured in T2 sequences of MRI. Further statistical analysis was applied to exclude gender and age effect on areas. RESULTS: The areas of putamen and cerebral peduncles were significantly reduced in patients with PD compared to the control bilaterally (p < 0.001). Enlargement of interpeduncular and ambient cisterns in patients was higher than in controls, and it was significant (p < 0.001). A correlation was not observed between measurement results and clinical characteristics of patients with PD. Only the cerebral peduncle area/ambient cistern width ratio was significantly correlated with disease duration positively (right r = 0.46 p = 0.012, left r = 0.389 p = 0.037). CONCLUSION: Clinicians should be careful with conventional MRIs of patients with idiopathic PD in practice. It may be different from controls without any neurological disorder, particularly putamen, cerebral peduncles, interpeduncular, and ambient cisterns.

The areas of putamen and cerebral peduncles were significantly reduced in patients with PDEnlargement of interpeduncular and right ambient cisterns were detected in patients with PDCerebral peduncle area/ambient cistern width ratio was significantly correlated with disease duration positivelyMRIs of patients with idiopathic PD may be different from controls without any neurological disorder, particularly putamen, cerebral peduncles, interpeduncular, and ambient cisterns.

Emotion dysregulation in migraine patients: can it be a hallmark the probability of the transformation from episodIc to chronic?

OBJECTIVE: The main aim of this study was to examine patients with migraine in terms of emotional dysregulation and to evaluate whether the emotion dysregulation is effective on chronicity in migraine. MATERIALS AND METHODS: A total of 85 migraine patients and 61 healthy participants were included in this study. All participants were evaluated using Migraine Disability Scale (MIDAS), Visual Analog Scale (VAS), Depression, Anxiety, and Stress Scale (DASS-21), Difficulties in Emotion Regulation Scale (DERS), Pain Catastrophizing Scale (PCS), and the Discomfort Intolerance Scale (DIS). Then, all results were compared between the migraine patients and healthy individuals. In addition, the migraine patients were separated into three groups as patients without an aura, patients with an aura and patients with chronic migraine and then their results were compared among them. Finally, the predictive markers of chronic migraine were explored using regression analyses. RESULTS: Among 85 migraine patients, the mean age was 31.5 (SD = 7.98); 83.5% were women. The total and subscale scores of DERS, PCS, DIS, and DASS-21 were significantly higher in patients than in healthy individuals (p < 0.01). Subscale scores of DERS, DIS, and DASS-21 in the chronic migraine patients were found to be higher than in the other two patient groups (p < 0.01). Logistic regression analysis showed that chronic migraine could be associated with 'lack of emotional clarity' (OR = 1.229; p = 0.042), 'lack of awareness' (OR = 1.187; p = 0.032), 'migraine associated disability' (OR = 1.128; p = 0.033), and 'stress' (OR = 1.292; p = 0.027). CONCLUSION: This study results showed that chronic migraine could be associated with the emotional dysregulation. To our knowledge, this study is the preliminary study in the literature and, therefore, new studies with large samples are needed.

Validity and reliability of the full cup test in patients with chronic low back pain.

OBJECTIVES: This study aims to determine the validity and reliability of the full cup test (FCT), evaluating the pain severity in patients with chronic low back pain. METHODS: A total of 100 patients (70 women and 30 men) aged over 18 years with mechanical low back pain were enrolled in the study. Demographic and clinical characteristics were recorded. Pain severity was evaluated using the visual analog scale (VAS) and FCT, the functional state was assessed by the Oswestry Disability Index (ODI), and the quality of life was assessed using the Nottingham Health Profile (NHP). FCT was performed on the 1st day by two independent observers (G1 and G2) and 3 days after the first application, patients were readministered the FCT by G1. RESULTS: The mean age of participants was 56.04±12.33 years and mean body mass index was 27.7±4.3 kg/m². The reliability of the FCT and intraclass correlation coefficient (ICC) was found to be 0.989 for intrarater compliance, ICC was found to be 0.984 for inter-rater compliance, and Cronbach's alpha reliability coefficient was α=0.994. External construct validity of the scale was confirmed with expected correlations with all subgroups of NHP except for social isolation, VAS and ODI (p<0.01). CONCLUSION: This study concludes that the FCT provides a reliable and valid instrument for measuring pain severity and loss of the function in patients with chronic mechanical back pain. We consider that FCT is a simple and easy test in patients with low education and advanced age.

Urinary 8-hydroxy-2'-deoxyguanosine level and plasma paraoxonase 1 activity with Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the most frequent cause of dementia and age is the most important risk factor for AD. Aging is associated with increased free radical production and oxidative stress plays an important role in the pathogenesis of AD. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a biomarker indicating oxidative DNA damage. Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme and prevents especially oxidation of low-density lipoproteins. The aim of this study is to measure urinary 8-OHdG levels and serum PON1 activity in patients with AD. METHODS: A total of 21 elderly patients diagnosed with moderate AD (10 men and 11 women, aged 76 ± 7.8 years) were included in the study. A total of 20 healthy elderly volunteers (11 men and nine women, aged 81 ± 7.2 years) were enrolled as a control group. Levels of urinary 8-OHdG, serum PON1 activity and lipid profile were determined in patients and controls. RESULTS: Urinary 8-OHdG levels were significantly increased, but serum PON1 activity was significantly decreased in patients compared to controls. Lipid profile did not show a difference between the groups. There was a negative correlation between 8-OHdG levels and PON1 activity only in the patient group (r=-0.536). Analytical performance characteristics of the methods used were satisfactory. CONCLUSIONS: In this study, evidence of increased oxidative DNA damage was determined in AD patients as well as decreased serum PON1 activity. Oxidant stress and oxidative DNA damage are important pathological processes in AD. The biomarkers, urinary 8-OHdG level and serum PON1 activity can be used to determine and monitor the status of patients with AD.

Coexistence of ankylosing spondylitis and multiple sclerosis.

Ankylosing spondylitis is reported to involve not only the joints but neurologic systems as well. The association of MS and AS has rarely been reported in the literature and epidemiological studies did not prove a definite relationship between these two conditions at present. We here describe a HLA-B 27 positive AS patient with MS symptoms and review the literature on the association of two diseases.

Vestibular migraine: A case report and review of the literature.

Vestibular migraine (VM) is one of the most common causes of episodic vertigo, but it can be missed in patients complaining of dizziness. This report describes the case of a 46-year-old woman with episodic vertigo attacks and a history of migrainous headaches. Some of the vertigo attacks were accompanied by a migraine. Gaze-induced nystagmus was present during attacks, but regressed with medication. Ear, nose, and throat evaluation; laboratory; imaging findings; and hearing test results were normal. Treatment with 500 mg valproic acid led to a rapid response in this case. VM should be considered in neurological examinations on the basis of clinical symptomatology.

First Admission Neutrophil-Lymphocyte Ratio May Indicate Acute Prognosis of Ischemic Stroke.

OBJECTIVES: Our study aimed to determine the relationship between serum periostin levels, and the neutrophil-lymphocyte ratio (NLR) with ischemic stroke subtypes, clinical stroke scales, and acute prognosis in patients with acute ischemic stroke. MATERIALS AND METHODS: Forty-two ischemic stroke patients and 39 age- and sex-matched healthy volunteers were included in our study. Demographic characteristics including age and gender were recorded. Blood serum periostin and NLR values were evaluated in the first 24 hours after admission. Serum periostin levels were compared with healthy controls of similar age and sex. Lesion localization was determined by cranial CT or diffusion MRI of the patients. Stroke scales were recorded on days 1 and 7 of hospitalization in the study group. RESULTS: The mean serum periostin levels were higher than in the control group, but no statistically significant difference was found. There was no correlation between serum periostin levels and prognosis of stroke. First admission NLRs were statistically higher than in the control group. The first admission NLRs were positively correlated with the first admission National Institute of Health Stroke Scale score and the day 7 modified Rankin score. CONCLUSION: Our study is the first study to evaluate both NLR and serum periostin levels in all types of acute ischemic stroke. While our study did not show that first admission serum periostin levels can be used as a biomarker in ischemic stroke, it did indicate that the first admission NLR can be used for acute prognosis of ischemic stroke.

In spontaneous intracerebral hematoma patients, prediction of the hematoma expansion risk and mortality risk using radiological and clinical markers and a newly developed scale.

Objective: In patients with spontaneous intracerebral hematoma (ICH), early-stage hematoma expansion has been associated with poor prognosis in literature. This study aimed to develop predictive parameter(s) as well as a new scale to define hematoma expansion and short-term prognosis in patients with ICH.Methods: In 46 patients with ICH, Glasgow Coma Scale (GCS) scores, non-contrast CT (NCCT) markers (hematoma volume on admission and follow-up, hypodensity, intraventricular hemorrhage, blend and island sign, BAT score), and modified Rankin Scale scores were evaluated for predicting the hematoma expansion risk and mortality risk. Furthermore, a newly developed scale called the 'HEMRICH scale' was constituted using the GCS score, hematoma volumes, and some NCCT markers.Results: Roc-Curve and Logistic Regression test results revealed that GCS score, initial hematoma volume value, hypodensity, intraventricular haemorrhage, BAT score, and HEMRICH scale score could be the best markers in predicting hematoma expansion risk whereas GCS score, intraventricular haemorrhage, BAT score, hematoma expansion, and HEMRICH scale score could be the best markers in predicting mortality risk (p = 0.01). Moreover, Factor analysis and Reliability test results showed that HEMRICH scale score could predict both hematoma expansion and mortality risks validly (Kaiser-Meyer-Olkin test value = 0.729) and reliably (Cronbach's alpha = 0.564).Conclusion: It was concluded that the GCS score, intraventricular haemorrhage, and BAT score could predict both hematoma expansion risk and mortality risk in the early stage in patients with ICH. Furthermore, it was suggested that the newly produced HEMRICH scale could be a valid and reliable scale for predicting both hematoma expansion and mortality risk.

Genome-wide association and whole exome sequencing studies reveal a novel candidate locus for restless legs syndrome.

INTRODUCTION: The restless legs syndrome (RLS) is a common heritable neurologic disorder which is characterized by an irresistible desire to move and unpleasant sensations in the legs. METHODS: We aim to identify new variants associated with RLS by performing genome-wide linkage and subsequent association analysis of forty member's family with history of RLS. RESULTS: We found evidence of linkage for three loci 7q21.11 (HLOD = 3.02), 7q21.13-7q21.3 (HLOD = 3.02) and 7q22.3 (HLOD = 3.09). Fine-mapping of those regions in association study using exome sequencing identified SEMA3A (p-value = 8.5·10-4), PPP1R9A (p-value = 7.2·10-4), PUS7 (p-value = 8.7·10-4), CDHR3 (p-value = 7.2·10-4), HBP1 (p-value = 1.5·10-4) and COG5 (p-value = 1.5·10-4) genes with p-values below significance threshold. CONCLUSION: Linkage analysis with subsequent association study of exome variants identified six new genes associated with RLS mapped on 7q21 and q22.

Peripheral nerve conductions in relapsing remitting multiple sclerosis (RRMS) patients.

PURPOSE: The purpose of this study was to investigate with Elektromioneurografija (EMNG) whether there is any affection on peripheral nerves in (RRMS) patients. MATERIAL AND METHOD: Motor and sensory nerve conductions were studied in the control group including 33 RRMS patients and 25 healthy individuals. Expanded Disability Status Scale (EDSS) scores, mean annual attack frequency, duration of disease and treatments of RRMS patients were recorded. RESULTS: There was a statistically significant (p < 0.05) elongation in motor distal latency of the right peroneal nerve, slowing in the left peroneal nerve conduction velocity, and an elongation in the F-wave response in the RRMS group compared to the control group. It was observed that motor nerve conduction velocities were slower, albeit not statistically significant, and F wave latencies were longer than control group. CONCLUSION: There are studies in the literature related to the association between MS and peripheral neuropathy. In this study, we found demyelinating type changes, differing significantly from the control group, in motor nerve conductions in RRMS patients. There may be demyelinating type affection in peripheral nervous system with common autoimmune mechanism in MS, a demyelinating disease of the central nervous system.

Detecting pain severity with full cup test in painful diabetic peripheral neuropathy.

OBJECTIVES: The aim of this study was to test the utility and validity of the full cup test (FCT) to assess the severity of pain in subjects with painful diabetic peripheral neuropathy (PDPN). METHODS: Subjects with diabetic PDPN were enrolled for this prospective, cross-sectional study. Other causes of PDPN and subjects with cognitive impairment were excluded. The diagnosis of neuropathic pain was made using the results of a physical examination and the Douleur Neuropathique 4 questionnaire. Pain severity was assessed with a FCT and a visual analog scale (VAS) administered before and after treatment. The correlation of FCT with VAS was evaluated to examine validity. RESULTS: A total of 43 (33 female, 10 male) subjects were included. The mean age was 61.9±8.25 years and the mean disease duration was 13.02±7.6 years. Type I diabetes mellitus (DM) was present in 2 (4.7%) subjects and Type II DM in 41 (95.3%) subjects. The mean glycated hemoglobin level was 8.9±1.9 mmol/mol. When the mean VAS and FCT scores were analyzed, the results were 6.7±2.05 and 66.35±23.2, respectively, pretreatment and 4.6±2.2 and 41.36±23.5 posttreatment, which were both statistically significant (p<0.001, p<0.001). The mean control period was 23.4 days (min-max: 15-30 days). The VAS and FCT scores in pretreatment and posttreatment demonstrated a high positive correlation (rs=0.86, p<0.001; rs=0.843, p<0.001). CONCLUSION: The FCT can be useful to detect pain severity in PDPN.

Why do multiple sclerosis and migraine coexist?

BACKGROUND: Migraine coexistence, which is high in multiple sclerosis (MS), is reported. To better understand the etiology of the coexistence of MS and migraine and the outcomes of this relationship, the vitamin D, vitamin D-binding protein (VITDBP), vitamin D receptor (VITDR), high-sensitivity C-reactive protein (hs-CRP), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant status (TAS), total oxidant status (TOS), and Oxidative Stress Index (OSI) values were examined in patients with the coexistence of relapsing-remitting multiple sclerosis (RRMS) and migraine. METHODS: This study was conducted between January 1, 2019, and July 25, 2019, at the neurology and biochemistry clinics of two different tertiary hospitals simultaneously. Overall, 50 RRMS patients with migraine, 50 RRMS patients without migraine, and 50 healthy volunteers were included in the study. The participants' vitamin D, VITDBP, VITDR, hs-CRP, SOD, CAT, GSH-Px, TAS, TOS, and OSI values were measured. RESULTS: The vitamin D and VITDR values of the RRMS patients with migraine were lower than those of the RRMS patients without migraine (respectively, p = 0.014, p < 0.001). There was no significant difference between the RRMS patients with and without migraine in terms of their VITDBP values (p = 0.570). The SOD, CAT, GSH-Px, and TAS values of the RRMS patients with migraine were lower than those without migraine (all p < 0.001). The hs-CRP and TOS values of the RRMS patients with migraine were higher than those without migraine (all p < 0.001). CONCLUSION: To the best of our knowledge, this is the first study on this topic to date. Based on the results, our study may shed light on the etiopathogenesis of the coexistence of MS and migraine and new treatments. However, more studies are needed to better understand the etiology of this relationship and its negative effects.

Brucella: a cause of peripheral neuropathy.

Brucellosis is a common infectious disease in Mediterranean countries. We evaluated the peripheral nerve involvement in patients with brucellosis. Thirty-eight patients with brucellosis were examined. Four of them were excluded because of B(12) deficiency and diabetes mellitus. Thirty-four patients were included. The average age was 43.08 +/- 15.3 years. Patients were divided into two groups according to the abnormality in their peripheral nervous system (PNS) examination. All patients underwent nerve conduction and needle electromyography EMG studies. Twenty normal healthy subjects were used as a control group. Axonal sensorimotor neuropathy was determined in 12 patients who also had abnormality in PNS examination. After 6 months of treatment, nerve conduction studies were nearly normal in these patients. The EMG findings of the remaining 22 patients were normal, as well as the clinical examination. However, the motor conduction velocities of median (p < 0.001), peroneal (p < 0.001), and ulnar (p < 0.05) nerves were decreased, F wave latencies were prolonged in the posterior tibial and peroneal nerve, and distal latency was also prolonged in the posterior tibial nerve (p < 0.05) when compared to healthy subjects. Sensory conduction velocities of the median (p < 0.001), ulnar and sural (p < 0.05) nerve were also decreased. Brucellosis may be considered as a cause of clinical or subclinical peripheral neuropathy and should be evaluated especially in endemic areas.

Cold effect in median nerve conductions in clinical carpal tunnel syndrome with normal nerve conduction studies.

Clinical diagnosis of carpal tunnel syndrome (CTS) is confirmed by nerve conduction studies (NCS). In some cases, NCS may be normal. We aimed to demonstrate changes of distal motor latency (DML) and nerve conduction velocity (NCV) pathology of demyelination in entrapment neuropathy with cold application in case of clinical CTS with normal NCS. This prospective, cross-sectional, randomise, case-control involved 15 patients (25 hands) with clinically definite unilateral or bilateral CTS and normal nerve conduction studies (NCS), and 11 controls (22 hands). Ice pack was applied to median nerve trasse at wirst with monitoring skin temperature. NCS of median nerve were examinated again. Increases of DML, decrease of velocity of median nerve were observed in two groups after post-cooling. The change in NCV was greater than the change in DML. Cold effect was evident in DML and NCV in the patient group. This could be sign of the demyelination pathology. We think that cold application is influential to determine electrophysiologic abnormalities in clinic CTS with normal NCS.

Intravenous theophylline decreases post-dural puncture headaches.

Post-dural puncture headache (PDPH) is a common complication of lumbar puncture. As invasive treatments for PDPH have known complications, pharmacologic management may be preferable. The aim of this study was to evaluate and to compare the efficacy of intravenous theophylline treatment for PDPH, in comparison with a placebo. We found that intravenous theophylline infusion was effective for decreasing the painfulness of PDPH compared with the control group. The mean visual analogue scale (VAS) value was 7.05+/-1.47 before the theophylline infusion and 2.88+/-2.31 after infusion. An average of 59.1% relief of pain was obtained in the group treated with theophylline infusion. The improvement in VAS in the study group was significant (p < 0.001), whereas that in the control group was not (p = 0.15). The mean VAS decrease after theophylline infusion was 4.17+/-2.03 in the study group and 0.41+/-0.71 in the control group; the difference in improvement between the groups was significant (p < 0.001). Intravenous theophylline infusion is an easy, rapid, minimally invasive, an effective treatment for PDPH. It may be attempted in PDPH patients before invasive techniques are used. To the best of our knowledge, this is the first report on the effect of intravenous infusion of theophylline compared with a placebo in the treatment of PDPH.

Power spectral analysis of heart rate variability: normal values of subjects over 60 years old.

Power spectral analysis of heart rate variability (HRV) provides a non-invasive method of estimating cardiac autonomic nerve activity. It has been reported that HRV decreases with age. The purpose of this study was to assess the values of and determine the reliability of HRV in healthy older people. The study found lower and highly variable values of HRV. It was concluded that the reliability of HRV in older subjects might need to be reinvestigated and only normalized values of HF and LF might be useful. Larger study groups and different recording periods of HRV are needed.

Visual evoked potentials in neurobrucellosis.

OBJECTIVE: To investigate whether visual evoked potentials (VEPs) are valuable for distinguishing between brucellosis with or without neurological involvement. METHODS: A total of 23 patients who were admitted to the Department of Infectious Diseases and Microbiology, and Neurology, Ministry of Health Ankara Education and Research Hospital, Ankara, Turkey between December 2004 and August 2005 with a diagnosis of brucellosis were included in this study. After a detailed neurological and ophthalmological examination, VEPs were recorded. The P100 latencies and amplitudes were compared between the group of brucellosis (n=17) and neurobrucellosis (n=6) patients. RESULTS: Although there was no difference in the mean P100 latencies between the groups (n=17 for brucellosis, and n=6 for neurobrucellosis) (p=0.38), the mean P100 amplitude in patients with neurobrucellosis was significantly lower (p=0.012). CONCLUSION: It could be emphasized that VEPs might reflect an underlying axonal pathology as a distinctive feature in neurobrucellosis.

Prevention of pro-depressant effect of L-arginine in the forced swim test by NG-nitro-L-arginine and [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one].

Previous studies have shown that l-arginine, the precursor of nitric oxide, has a dual effect (antidepressant and pro-depressant) in the forced swim test. The aim of the present study was to investigate whether nitric oxide-cGMP pathway was involved in this dual effect. Porsolt swim test was conducted to resemble the symptomatology of major depressive disorder. An open field locomotor activity test was also used. L-arginine exerted a U-shape effect in the forced swim test: doses of 30, 100, 300, and 1000 mg/kg caused no alteration, statistically significant reduction, no alteration, and non-significant enhancement, respectively. Neither N(G)-nitro-L-arginine (NNA) nor [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one] (ODQ) at doses of 3 mg/kg was found to be effective in the forced swim test, whereas 10 mg/kg ODQ significantly reduced the immobility time. In the presence of NNA, the antidepressant and pro-depressant effects of L-arginine disappeared, however, only the pro-depressant component of l-arginine effect was prevented by ODQ (3 and 10 mg/kg). Saline, the solvent of L-arginine and NNA, and dimethyl sulfoxide (15% in saline), the solvent of ODQ, had no effect on the duration of immobility. None of the drugs or solvents used in the present study had any effect on locomotor activity over the dose range applied. The results show that L-arginine exerts its paradoxical effects by producing nitric oxide and that cGMP seems to have a role only in the pro-depressant component.