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Papers by Maria Vital

Behavioural Brain Research, Oct 1, 2019

Anxiety-like behavior induced by 6-OHDA animal model of Parkinson's disease may be related to a d... more Anxiety-like behavior induced by 6-OHDA animal model of Parkinson's disease may be related to a dysregulation of neurotransmitter systems in brain areas related to anxiety.

Brain Research Bulletin, 2021

The most common features of Parkinson's disease (PD) are motor impairments, but many patients... more The most common features of Parkinson's disease (PD) are motor impairments, but many patients also present depression and memory impairment. Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has been shown to be effective in patients with treatment-resistant major depression. Thus, the present study evaluated the action of ketamine on memory impairment and depressive-like behavior in an animal model of PD. Male Wistar rats received a bilateral infusion of 6 μg/side 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNc). Short-term memory was evaluated by the social recognition test, and depressive-like behaviors were evaluated by the sucrose preference and forced swimming tests (FST). Drug treatments included vehicle (i.p., once a week); ketamine (5, 10 and 15 mg/kg, i.p., once a week); and imipramine (20 mg/kg, i.p., daily). The treatments were administered 21 days after the SNc lesion and lasted for 28 days. The SNc lesion impaired short-term social memory, and all ketamine doses reversed the memory impairment and anhedonia (reduction of sucrose preference) induced by 6-OHDA. In the FST, 6-OHDA increased immobility, and all doses of ketamine and imipramine reversed this effect. The anti-immobility effect of ketamine was associated with an increase in swimming but not in climbing, suggesting a serotonergic effect. Ketamine and imipramine did not reverse the 6-OHDA-induced reduction in tyrosine hydroxylase immunohistochemistry in the SNc. In conclusion, ketamine reversed depressive-like behaviors and short-term memory impairment in rats with SNc bilateral lesions, indicating a promising profile for its use in PD patients.

Journal of Alzheimer's Disease Reports, 2020

Background: It has been studied that nutrition can influence Alzheimer’s disease (AD) onset and p... more Background: It has been studied that nutrition can influence Alzheimer’s disease (AD) onset and progression. Some studies on rodents using intraventricular streptozotocin (STZ) injection showed that this toxin changes cerebral glucose metabolism and insulin signaling pathways. Objective: The aim of the present study was to evaluate whether a nutritional formulation could reduce cognitive impairment in STZ-induced animals. Methods: The rats were randomly divided into two groups: sham and STZ. The STZ group received a single bilateral STZ-ICV injection (1 mg/kg). The sham group received a bilateral ICV injection of 0.9% saline solution. The animals were treated with AZ1 formulation (Instanth® NEO, Prodiet Medical Nutrition) (1 g/kg, PO) or its vehicle (saline solution) for 30 days, once a day starting one day after the stereotaxic surgery (n = 6–10). The rats were evaluated using the open field test to evaluate locomotor activity at day 27 after surgery. Cognitive performance was eval...

Revista Brasileira de Psiquiatria, 2018

Objective: Amantadine blocks N-methyl-D-aspartate (NMDA) receptors and has dopaminergic and norad... more Objective: Amantadine blocks N-methyl-D-aspartate (NMDA) receptors and has dopaminergic and noradrenergic action, a neurochemical profile that suggests its potential as an antidepressant drug. We conducted a systematic review of preclinical and clinical studies addressing the effects of amantadine in animal models of depression and in patients with depression. Methods: PubMed, Science Direct, and Web of Science were searched up to September 1, 2017 to identify clinical and preclinical studies. The following search terms were used: ''amantadine AND depress*''; ''amantadine AND mood''; ''amantadine AND animal models AND antidepres*''; and ''amantadine AND (forced swim, learned helplessness, reserpine, chronic mild stress, anhedonia, sucrose preference).'' Results: Amantadine had antidepressant-like effects in animal models and appeared to potentiate the antidepressant effects of other antidepressants. These preclinical findings have received some support from the results of small open-label clinical trials, suggesting that amantadine can reduce depressive symptomatology and potentiate the antidepressant effects of monoaminergic drugs. In addition to its glutamatergic and dopaminergic effects, the potential antidepressant-like effects of amantadine have been linked to molecular and cellular actions, such as increased expression of neurotrophic factors (e.g., brain-derived neurotrophic factor), activation of s 1 receptors, decreased corticosterone levels, and decreased inflammatory response to stress. Conclusion: Amantadine is an interesting candidate as new antidepressant drug for the treatment of depression.

ACS Omega, 2020

The beneficial effect of polyphenols and magnesium(II) against oxidative stress motivated our res... more The beneficial effect of polyphenols and magnesium(II) against oxidative stress motivated our research group to explore the antioxidant activity of phenMgIso, an aqueous soluble magnesium(II) complex containing 1,10-phenanthroline (phen) and isovanillic acid (Iso) as ligands. Combined electrospray ionization−mass spectrometry and DOSY-NMR techniques identified two complexes in methanolic solution: hexacoordinated [Mg(phen) 2 (Iso)] + and tetracoordinated [Mg(phen)-(Iso)] +. The cyclic voltammogram of phenMgIso in the anodic region showed a cyclic process that interrupts the isovanillic acid degradation, probably by stabilization of the corresponding phenoxyl radical via complexation with Mg(II), which is interesting for antioxidant applications. phenMgIso competes with 2,2,6,6-tetramethylpiperidine by 1 O 2 with IC 50 (1 O 2) = 15 μg m −1 and with nitrotetrazolium blue chloride by superoxide ions (IC 50 (O 2 •−) = 3.6 μg mL −1). Exposure of both zebrafish (2 mg L −1) and wistar male rats (3 mg kg −1 day −1 dose for 21 days) to phenMgIso does not cause mortality or visual changes compared with the respective control groups, thus phenMgIso could be considered safe under the conditions of this study. Moreover, no significant changes in comparison to both control groups were observed in the biochemical parameters on the brain-acetylcholinesterase activity, digestive tract enzyme catalase, and glutathione-S-transferase. Conversely, the performance of superoxide dismutase activity in wistar male rats increased in the presence of a complex, resulting in enhanced capacity of rats for superoxide radical enzymatic scavenging. The synergistic action of phenMgIso may be explained by the strong electrostatic interaction between Mg(II) and the O,O(phenolate) group, which makes the Iso ligand easier to oxidize and deprotonate, generating a cyclic stable species under oxidative conditions.

European Neuropsychopharmacology, 2011

European Neuropsychopharmacology, 2011

European Neuropsychopharmacology, 2013

European Neuropsychopharmacology, 2011

Neurochemical Research, 2010

The current investigation compared intranigral lipopolysaccharide (LPS), 1-methyl-4-phenyl-1,2,3,... more The current investigation compared intranigral lipopolysaccharide (LPS), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) administrations, in the light of neurochemical, behavioral and endogenous antioxidant glutathione alterations. All the results were collected 1, 3 and 7 days after the lesions. LPS produced a delayed reduction of striatal dopamine, whereas homovanillic acid was drastically increased at the first time-point. Comparatively, MPTP promoted dopamine reduction 3 and 7 days with increase of homovanillic acid. Whilst, 6-OHDA generated initial increase of dopamine and homovanillic acid followed by subsequent decrease of this neurotransmitter accompanied by reductions of dopamine metabolites at the same periods. Furthermore, nigral glutathione demonstrated to be a far more sensitive target for LPS than for MPTP or 6-OHDA. Behavioral data indicated impairments induced by MPTP, 6-OHDA but not LPS. In conclusion, it is suggested that intranigral LPS can provide new insights about neuroinflammation, simulating features of the pre-motor phase of Parkinson's disease.

Neurobiology of Learning and Memory, 2014

This study examined the effects of bilateral excitotoxic lesions of the nucleus accumbens core (N... more This study examined the effects of bilateral excitotoxic lesions of the nucleus accumbens core (NAc-co), dorsomedial striatum (DMS) or dorsolateral striatum (DLS) of rats on the learning and extinction of Pavlovian and instrumental components of conditioned avoidance responses (CARs). None of the lesions caused sensorimotor deficits that could affect locomotion. Lesions of the NAc-co, but not DMS or DLS, decreased unconditioned and conditioned freezing. The NAc-co and DLS lesioned rats learned the 2-way active avoidance task more slowly. These results suggest: (i) CARs depend on both Pavlovian and instrumental learning; (ii) learning the Pavlovian component of CARs depends on the NAc-co; learning the instrumental component of CARs depends on the DLS, NAc and DMS; (iii) although the NAc-co is also needed for learning the instrumental component, it is not clear whether it plays a role in learning the instrumental component per se or if it simply allows learning of the Pavlovian component which is a precondition for learning the instrumental component; (iv) we did not find evidence that the DMS and DLS play the same roles in habit and goaldirected aspects of the instrumental component of CARs as observed in appetitive motivated instrumental responding.

Journal of Neural Transmission, 2014

Beyond the current hypothesis of depression, several new biological substrates have been proposed... more Beyond the current hypothesis of depression, several new biological substrates have been proposed for this disorder. The present study investigated whether the anti-inflammatory drugs celecoxib and piroxicam have antidepressant activity in animal models of depression. After acute administration, we observed antidepressant-like effects of celecoxib (10 mg/kg) and piroxicam (10 mg/kg) in the modified forced swim test in rats. Piroxicam increased serotonin and norepinephrine levels in the hippocampus. Prolonged (21-day) treatment with celecoxib (10 mg/kg) and piroxicam (10 mg/kg) rescued sucrose preference in a chronic mild stress model of depression. Additionally, the chronic mild stress-induced reduction of hippocampal glutathione was prevented by treatment with celecoxib and piroxicam. Superoxide dismutase in the hippocampus was increased after chronic mild stress compared with the non-stressed saline group. The non-stressed celecoxib and piroxicam groups and stressed piroxicam group exhibited an increase in hippocampal superoxide dismutase activity compared with the stressed saline group. Lipid hydroperoxide was increased in the stressed group treated with vehicle and non-stressed group treated with imipramine but not in the stressed groups treated with celecoxib and piroxicam. These results suggest that the antidepressant-like effects of anti-inflammatory drugs might be attributable to enhanced antioxidant defenses and attenuated oxidative stress in the hippocampus.

Experimental Neurology, 2005

The present study investigated the motor response and possible changes in binding to D 1 and D 2 ... more The present study investigated the motor response and possible changes in binding to D 1 and D 2 receptors after intra-nigral 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) infusion on rats. The results indicated that MPTP-lesioned rats exhibited a significant reduction in locomotion and rearing frequencies observed in an open field 24 h after surgery. However, at 7 and 14 days after surgery the MPTP-lesioned rats showed a significant increase in locomotion in comparison to the control groups, as well as a decrease in immobility time. In addition, 21 days after surgery the behavioral measurements were unaltered by these procedures. Moreover, latency in initiating movement and catalepsy were unchanged by this neurotoxin on the same days of observation. An autoradiography approach indicated that there was a reduction in [ 3 H]SCH 23390 binding in substantia nigra pars compacta (SNpc), substantia nigra pars reticulata (SNpr) and ventrolateral striatum in MPTP-treated rats 21 days after the surgery. [ 3 H]raclopride binding remained unaltered by the MPTP treatment. These results suggest that compensatory plastic changes occur in D 1 dopamine receptors after partial lesion of nigral dopaminergic neurons. These alterations might be related to the occurrence and recovery of motor impairment observed in MPTP-lesioned rats.

European Neuropsychopharmacology, 2013

European Neuropsychopharmacology, 2011

European Neuropsychopharmacology, 2003

European Journal of Pharmacology, 2007

The present study investigated the effects of the selective cyclooxygenase-2 (COX-2) inhibitor pa... more The present study investigated the effects of the selective cyclooxygenase-2 (COX-2) inhibitor parecoxib (Bextra™) in the prevention of motor and cognitive impairments observed in rats after an intranigral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a model of the early phase of Parkinson's disease. The treatment with parecoxib (10 mg/kg) administered prior to the surgery and daily (2 mg/kg) for the subsequent 21 days, prevented the MPTP-treated rats from presenting decreased locomotor and exploratory behavior, increased immobility, and impairment while performing the cued version of the Morris water maze. Furthermore, parecoxib treatment also significantly prevented the reduction of tyrosine hydroxylase protein expression in the substantia nigra (7, 14 and 21 days after surgery), and in the striatum (14 and 21 days after surgery) as immunodetected by western blotting. These results strongly suggest that parecoxib exerts a neuroprotective effect on motor, tyrosine hydroxylase expression, and cognitive functions as it prevents their impairments within the confines of this animal model of the early phase of Parkinson's disease.

Behavioural Brain Research, Oct 1, 2019

Anxiety-like behavior induced by 6-OHDA animal model of Parkinson's disease may be related to a d... more Anxiety-like behavior induced by 6-OHDA animal model of Parkinson's disease may be related to a dysregulation of neurotransmitter systems in brain areas related to anxiety.

Brain Research Bulletin, 2021

The most common features of Parkinson's disease (PD) are motor impairments, but many patients... more The most common features of Parkinson's disease (PD) are motor impairments, but many patients also present depression and memory impairment. Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has been shown to be effective in patients with treatment-resistant major depression. Thus, the present study evaluated the action of ketamine on memory impairment and depressive-like behavior in an animal model of PD. Male Wistar rats received a bilateral infusion of 6 μg/side 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNc). Short-term memory was evaluated by the social recognition test, and depressive-like behaviors were evaluated by the sucrose preference and forced swimming tests (FST). Drug treatments included vehicle (i.p., once a week); ketamine (5, 10 and 15 mg/kg, i.p., once a week); and imipramine (20 mg/kg, i.p., daily). The treatments were administered 21 days after the SNc lesion and lasted for 28 days. The SNc lesion impaired short-term social memory, and all ketamine doses reversed the memory impairment and anhedonia (reduction of sucrose preference) induced by 6-OHDA. In the FST, 6-OHDA increased immobility, and all doses of ketamine and imipramine reversed this effect. The anti-immobility effect of ketamine was associated with an increase in swimming but not in climbing, suggesting a serotonergic effect. Ketamine and imipramine did not reverse the 6-OHDA-induced reduction in tyrosine hydroxylase immunohistochemistry in the SNc. In conclusion, ketamine reversed depressive-like behaviors and short-term memory impairment in rats with SNc bilateral lesions, indicating a promising profile for its use in PD patients.

Journal of Alzheimer's Disease Reports, 2020

Background: It has been studied that nutrition can influence Alzheimer’s disease (AD) onset and p... more Background: It has been studied that nutrition can influence Alzheimer’s disease (AD) onset and progression. Some studies on rodents using intraventricular streptozotocin (STZ) injection showed that this toxin changes cerebral glucose metabolism and insulin signaling pathways. Objective: The aim of the present study was to evaluate whether a nutritional formulation could reduce cognitive impairment in STZ-induced animals. Methods: The rats were randomly divided into two groups: sham and STZ. The STZ group received a single bilateral STZ-ICV injection (1 mg/kg). The sham group received a bilateral ICV injection of 0.9% saline solution. The animals were treated with AZ1 formulation (Instanth® NEO, Prodiet Medical Nutrition) (1 g/kg, PO) or its vehicle (saline solution) for 30 days, once a day starting one day after the stereotaxic surgery (n = 6–10). The rats were evaluated using the open field test to evaluate locomotor activity at day 27 after surgery. Cognitive performance was eval...

Revista Brasileira de Psiquiatria, 2018

Objective: Amantadine blocks N-methyl-D-aspartate (NMDA) receptors and has dopaminergic and norad... more Objective: Amantadine blocks N-methyl-D-aspartate (NMDA) receptors and has dopaminergic and noradrenergic action, a neurochemical profile that suggests its potential as an antidepressant drug. We conducted a systematic review of preclinical and clinical studies addressing the effects of amantadine in animal models of depression and in patients with depression. Methods: PubMed, Science Direct, and Web of Science were searched up to September 1, 2017 to identify clinical and preclinical studies. The following search terms were used: ''amantadine AND depress*''; ''amantadine AND mood''; ''amantadine AND animal models AND antidepres*''; and ''amantadine AND (forced swim, learned helplessness, reserpine, chronic mild stress, anhedonia, sucrose preference).'' Results: Amantadine had antidepressant-like effects in animal models and appeared to potentiate the antidepressant effects of other antidepressants. These preclinical findings have received some support from the results of small open-label clinical trials, suggesting that amantadine can reduce depressive symptomatology and potentiate the antidepressant effects of monoaminergic drugs. In addition to its glutamatergic and dopaminergic effects, the potential antidepressant-like effects of amantadine have been linked to molecular and cellular actions, such as increased expression of neurotrophic factors (e.g., brain-derived neurotrophic factor), activation of s 1 receptors, decreased corticosterone levels, and decreased inflammatory response to stress. Conclusion: Amantadine is an interesting candidate as new antidepressant drug for the treatment of depression.

ACS Omega, 2020

The beneficial effect of polyphenols and magnesium(II) against oxidative stress motivated our res... more The beneficial effect of polyphenols and magnesium(II) against oxidative stress motivated our research group to explore the antioxidant activity of phenMgIso, an aqueous soluble magnesium(II) complex containing 1,10-phenanthroline (phen) and isovanillic acid (Iso) as ligands. Combined electrospray ionization−mass spectrometry and DOSY-NMR techniques identified two complexes in methanolic solution: hexacoordinated [Mg(phen) 2 (Iso)] + and tetracoordinated [Mg(phen)-(Iso)] +. The cyclic voltammogram of phenMgIso in the anodic region showed a cyclic process that interrupts the isovanillic acid degradation, probably by stabilization of the corresponding phenoxyl radical via complexation with Mg(II), which is interesting for antioxidant applications. phenMgIso competes with 2,2,6,6-tetramethylpiperidine by 1 O 2 with IC 50 (1 O 2) = 15 μg m −1 and with nitrotetrazolium blue chloride by superoxide ions (IC 50 (O 2 •−) = 3.6 μg mL −1). Exposure of both zebrafish (2 mg L −1) and wistar male rats (3 mg kg −1 day −1 dose for 21 days) to phenMgIso does not cause mortality or visual changes compared with the respective control groups, thus phenMgIso could be considered safe under the conditions of this study. Moreover, no significant changes in comparison to both control groups were observed in the biochemical parameters on the brain-acetylcholinesterase activity, digestive tract enzyme catalase, and glutathione-S-transferase. Conversely, the performance of superoxide dismutase activity in wistar male rats increased in the presence of a complex, resulting in enhanced capacity of rats for superoxide radical enzymatic scavenging. The synergistic action of phenMgIso may be explained by the strong electrostatic interaction between Mg(II) and the O,O(phenolate) group, which makes the Iso ligand easier to oxidize and deprotonate, generating a cyclic stable species under oxidative conditions.

European Neuropsychopharmacology, 2011

European Neuropsychopharmacology, 2011

European Neuropsychopharmacology, 2013

European Neuropsychopharmacology, 2011

Neurochemical Research, 2010

The current investigation compared intranigral lipopolysaccharide (LPS), 1-methyl-4-phenyl-1,2,3,... more The current investigation compared intranigral lipopolysaccharide (LPS), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) administrations, in the light of neurochemical, behavioral and endogenous antioxidant glutathione alterations. All the results were collected 1, 3 and 7 days after the lesions. LPS produced a delayed reduction of striatal dopamine, whereas homovanillic acid was drastically increased at the first time-point. Comparatively, MPTP promoted dopamine reduction 3 and 7 days with increase of homovanillic acid. Whilst, 6-OHDA generated initial increase of dopamine and homovanillic acid followed by subsequent decrease of this neurotransmitter accompanied by reductions of dopamine metabolites at the same periods. Furthermore, nigral glutathione demonstrated to be a far more sensitive target for LPS than for MPTP or 6-OHDA. Behavioral data indicated impairments induced by MPTP, 6-OHDA but not LPS. In conclusion, it is suggested that intranigral LPS can provide new insights about neuroinflammation, simulating features of the pre-motor phase of Parkinson's disease.

Neurobiology of Learning and Memory, 2014

This study examined the effects of bilateral excitotoxic lesions of the nucleus accumbens core (N... more This study examined the effects of bilateral excitotoxic lesions of the nucleus accumbens core (NAc-co), dorsomedial striatum (DMS) or dorsolateral striatum (DLS) of rats on the learning and extinction of Pavlovian and instrumental components of conditioned avoidance responses (CARs). None of the lesions caused sensorimotor deficits that could affect locomotion. Lesions of the NAc-co, but not DMS or DLS, decreased unconditioned and conditioned freezing. The NAc-co and DLS lesioned rats learned the 2-way active avoidance task more slowly. These results suggest: (i) CARs depend on both Pavlovian and instrumental learning; (ii) learning the Pavlovian component of CARs depends on the NAc-co; learning the instrumental component of CARs depends on the DLS, NAc and DMS; (iii) although the NAc-co is also needed for learning the instrumental component, it is not clear whether it plays a role in learning the instrumental component per se or if it simply allows learning of the Pavlovian component which is a precondition for learning the instrumental component; (iv) we did not find evidence that the DMS and DLS play the same roles in habit and goaldirected aspects of the instrumental component of CARs as observed in appetitive motivated instrumental responding.

Journal of Neural Transmission, 2014

Beyond the current hypothesis of depression, several new biological substrates have been proposed... more Beyond the current hypothesis of depression, several new biological substrates have been proposed for this disorder. The present study investigated whether the anti-inflammatory drugs celecoxib and piroxicam have antidepressant activity in animal models of depression. After acute administration, we observed antidepressant-like effects of celecoxib (10 mg/kg) and piroxicam (10 mg/kg) in the modified forced swim test in rats. Piroxicam increased serotonin and norepinephrine levels in the hippocampus. Prolonged (21-day) treatment with celecoxib (10 mg/kg) and piroxicam (10 mg/kg) rescued sucrose preference in a chronic mild stress model of depression. Additionally, the chronic mild stress-induced reduction of hippocampal glutathione was prevented by treatment with celecoxib and piroxicam. Superoxide dismutase in the hippocampus was increased after chronic mild stress compared with the non-stressed saline group. The non-stressed celecoxib and piroxicam groups and stressed piroxicam group exhibited an increase in hippocampal superoxide dismutase activity compared with the stressed saline group. Lipid hydroperoxide was increased in the stressed group treated with vehicle and non-stressed group treated with imipramine but not in the stressed groups treated with celecoxib and piroxicam. These results suggest that the antidepressant-like effects of anti-inflammatory drugs might be attributable to enhanced antioxidant defenses and attenuated oxidative stress in the hippocampus.

Experimental Neurology, 2005

The present study investigated the motor response and possible changes in binding to D 1 and D 2 ... more The present study investigated the motor response and possible changes in binding to D 1 and D 2 receptors after intra-nigral 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) infusion on rats. The results indicated that MPTP-lesioned rats exhibited a significant reduction in locomotion and rearing frequencies observed in an open field 24 h after surgery. However, at 7 and 14 days after surgery the MPTP-lesioned rats showed a significant increase in locomotion in comparison to the control groups, as well as a decrease in immobility time. In addition, 21 days after surgery the behavioral measurements were unaltered by these procedures. Moreover, latency in initiating movement and catalepsy were unchanged by this neurotoxin on the same days of observation. An autoradiography approach indicated that there was a reduction in [ 3 H]SCH 23390 binding in substantia nigra pars compacta (SNpc), substantia nigra pars reticulata (SNpr) and ventrolateral striatum in MPTP-treated rats 21 days after the surgery. [ 3 H]raclopride binding remained unaltered by the MPTP treatment. These results suggest that compensatory plastic changes occur in D 1 dopamine receptors after partial lesion of nigral dopaminergic neurons. These alterations might be related to the occurrence and recovery of motor impairment observed in MPTP-lesioned rats.

European Neuropsychopharmacology, 2013

European Neuropsychopharmacology, 2011

European Neuropsychopharmacology, 2003

European Journal of Pharmacology, 2007

The present study investigated the effects of the selective cyclooxygenase-2 (COX-2) inhibitor pa... more The present study investigated the effects of the selective cyclooxygenase-2 (COX-2) inhibitor parecoxib (Bextra™) in the prevention of motor and cognitive impairments observed in rats after an intranigral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a model of the early phase of Parkinson's disease. The treatment with parecoxib (10 mg/kg) administered prior to the surgery and daily (2 mg/kg) for the subsequent 21 days, prevented the MPTP-treated rats from presenting decreased locomotor and exploratory behavior, increased immobility, and impairment while performing the cued version of the Morris water maze. Furthermore, parecoxib treatment also significantly prevented the reduction of tyrosine hydroxylase protein expression in the substantia nigra (7, 14 and 21 days after surgery), and in the striatum (14 and 21 days after surgery) as immunodetected by western blotting. These results strongly suggest that parecoxib exerts a neuroprotective effect on motor, tyrosine hydroxylase expression, and cognitive functions as it prevents their impairments within the confines of this animal model of the early phase of Parkinson's disease.

Brazilian Journal of Medical and Biological Research, 2003

The objective of the present study was to evaluate the reliability and clinical utility of a Port... more The objective of the present study was to evaluate the reliability and clinical utility of a Portuguese version of the Abnormal Involuntary Movements Scale (AIMS). Videotaped interviews with 16 psychiatric inpatients treated with antipsychotic drugs for at least 5 years were evaluated. Reliability was assessed by the intraclass correlation coefficient
(ICC) between three raters, two with and one without clinical
training in psychopathology. Clinical utility was assessed by the
difference between the scores of patients with (N = 11) and without (N = 5) tardive dyskinesia (TD). Patients with TD exhibited a higherseverity of global evaluation by the AIMS (sum of scores: 4.2 ± 0.9 vs 0.4 ± 0.2; score on item 8: 2.3 ± 0.3 vs 0.4 ± 0.2, TD vs controls). The ICC for the global evaluation was fair between the two skilled raters (0.58-0.62) and poor between these raters and the rater without clinical experience (0.05-0.29). Thus, we concluded that the Portuguese version of the AIMS shows an acceptable inter-rater reliability, but only between clinically skilled raters, and that it is clinically useful.