The preventive effects of ascorbic acid supplementation on locomotor and acetylcholinesterase activity in an animal model of schizophrenia induced by ketamine

ABSTRACT Studies have shown that schizophrenic patients seem to have nutritional deficiencies. Ascorbic acid (AA) has an important antioxidant effect and neuromodulatory properties. The aim of this study was to evaluate the effects of AA on locomotor activity and the acetylcholinesterase activity (AChE) in an animal model of schizophrenia (SZ). Rats were supplemented with AA (0.1, 1, or 10 mg/kg), or water for 14 days (gavage). Between the 9th and 15th days, the animals received Ketamine (Ket) (25 mg/kg) or saline (i.p). After the last administration (30 min) rats were subjected to the behavioral test. Brain structures were dissected for biochemical analysis. There was a significant increase in the locomotor activity in Ket treated. AA prevented the hyperlocomotion induced by ket. Ket also showed an increase of AChE activity within the prefrontal cortex and striatum prevented by AA. Our data indicates an effect for AA in preventing alterations induced by Ket in an animal model of SZ, suggesting that it may be an adjuvant approach for the development of new therapeutic strategies within this psychiatric disorder.

Effects and molecular mechanism of chitosan-coated levodopa nanoliposomes on behavior of dyskinesia rats

BACKGROUND: Chitosan, the N-deacetylated derivative of chitin, is a cationic polyelectrolyte due to the presence of amino groups, one of the few occurring in nature. The use of chitosan in protein and drug delivery systems is being actively researched and reported in the literature RESULTS: In this study, we used chitosan-coated levodopa liposomes to investigate the behavioral character and the expression of phosphorylated extracellular signal-regulated kinase (ERK1/2), dopamine- and cAMP-regulated phos-phoprotein of 32 kDa (DARPP-32) and FosB/AFosB in striatum of rat model of levodopa-induced dyskinesia (LID). We found that scores of abnormal involuntary movement (AIM) decreased significantly in liposome group (P < 0.05), compared with levodopa group. Levels of phospho-ERK1/2, phospho-Thr34 DARPP-32 and FosB/AFosB in striatum decreased significantly in liposome group lesion side compared with levodopa group (P < 0.05). However, both of two groups above have significantly differences compared with the control group (P < 0.05). CONCLUSION: Chitosan-coated levodopa liposomes may be useful in reducing dyskinesias inducing for Parkinson disease. The mechanism might be involved the pathway of signaling molecular phospho-ERK1/2, phospho-Thr34 DARPP-32 and AFosB in striatum

Características clínicas y epidemiológicas del trauma ocular en menores de 14 años / Clinical and epidemiological characteristics of ocular trauma in children under 14 years of age

El trauma ocular pediátrico es frecuente y es la principal causa de ceguera unilateral no congénita. La información en países en vías de desarrollo es escasa. El objetivo de esta serie de casos es describir las características clínicas y epidemiológicas del trauma ocular en niños menores de 14 años que consultaron al Hospital Dr. Rodolfo Robles Val verde en la Ciudad de Guatemala durante el año 2010. Se incluyeron 119 pacientes en el estudio. El género masculino en edad escolar (7-9 años) fue el más comprometido. El trauma más común fue el de globo cerrado. Los objetos más frecuentes causantes de la lesión fueron madera, juguetes y químicos. La vivienda fue el lugar donde más ocurrió el trauma. Se intervinieron 21 pacientes. Son necesarios programas de educación y prevención.

Pediatric ocular trauma is common and the leading cause of non congenital unilateral blindness. The information in developing countries is scarce. The objective of this case series is to describe clinical and epidemiological characteristics of ocular trauma in children under 14 years of age who visited Hospital Dr. Rodolfo Robles Valverde in Guatemala City in 2010. In this study 119 patients were included. School-aged (7-9 years) male gender was the most affected. Closed globe injury was the commonest. The most frequent objects causing the lesions were: wooden objects, toys and chemicals. Trauma occurred most frequently at home. Twenty one of the patients were surgically intervened. Education and prevention programs for pediatric ocular trauma are necessary.

Atorvastatin protects GABAergic and dopaminergic neurons in the nigrostriatal system in an experimental rat model of transient focal cerebral ischemia / La atorvastatina protege las neuronas gabérgicas y dopaminérgicas del sistema nigroestriatal en un modelo experimental de isquemia cerebral focal transitoria en ratas

Introduction: Cerebral ischemia is the third leading cause of death and the primary cause of permanent disability worldwide. Atorvastatin is a promising drug with neuroprotective effects that may be useful for the treatment of stroke. However, the effects of atorvastatin on specific neuronal populations within the nigrostriatal system following cerebral ischemia are unknown. Objective: To evaluate the effects of atorvastatin on dopaminergic and GABAergic neuronal populations in exofocal brain regions in a model of transient occlusion of the middle cerebral artery. Materials and methods: Twenty-eight male eight-week-old Wistar rats were used in this study. Both sham and ischemic rats were treated with atorvastatin (10 mg/kg) or carboxymethylcellulose (placebo) by gavage at 6, 24, 48 and 72 hours post-reperfusion. We analyzed the immunoreactivity of glutamic acid decarboxylase and tyrosine hydroxylase in the globus pallidus, caudate putamen and substantia nigra. Results: We observed neurological damage and cell loss in the caudate putamen following ischemia. We also found an increase in tyrosine hydroxylase immunoreactivity in the medial globus pallidus and substantia nigra reticulata, as well as a decrease in glutamic acid decarboxylase immunoreactivity in the lateral globus pallidus in ischemic animals treated with a placebo. However, atorvastatin treatment was able to reverse these effects, significantly decreasing tyrosine hydroxylase levels in the medial globus pallidus and substantia nigra reticulata and significantly increasing glutamic acid decarboxylase levels in the lateral globus pallidus. Conclusion: Our data suggest that post-ischemia treatment with atorvastatin can have neuro-protective effects in exofocal regions far from the ischemic core by modulating the GABAergic and dopaminergic neuronal populations in the nigrostriatal system, which could be useful for preventing neurological disorders.

Introducción. La isquemia cerebral es la tercera causa de muerte y la primera de discapacidad permanente en el mundo. La atorvastatina es un fármaco neuroprotector prometedor para el tratamiento de la apoplejía; sin embargo, su acción sobre las poblaciones neuronales del sistema nigroestriatal después de la isquemia aún se desconoce. Objetivo. Evaluar el efecto de la atorvastatina sobre poblaciones gabérgicas y dopaminérgicas en regiones exofocales en un modelo de oclusión transitoria de la arteria cerebral media. Materiales y métodos. Se utilizaron 28 ratas Wistar macho de ocho semanas de edad. Los ejemplares con isquemia simulada y los ejemplares sometidos a isquemia fueron tratados con atorvastatina (10 mg/kg) y carboximetilcelulosa (placebo) administrados por medio de sonda a las 6, 24, 48 y 72 horas después de la reperfusión. Se analizó la inmunorreacción de la descarboxilasa del ácido glutámico y de la tirosina hidroxilasa en el globo pálido, el putamen caudado y la sustancia negra. Resultados. Los datos confirmaron el daño neurológico y la pérdida celular en el putamen caudado. Se incrementó la inmunorreacción de la tirosina hidroxilasa en el globo pálido medial y la sustancia negra pars reticulata , disminuyendo la inmunorreacción de la descarboxilasa del ácido glutámico en el globo pálido lateral de los animales isquémicos tratados con placebo; sin embargo, el tratamiento con atorvastatina pudo revertirla, lo que logró una disminución significativa de la tirosina hidroxilasa en el globo pálido medial y la sustancia negra pars reticulata y aumentando los niveles de descarboxilasa del ácido glutámico en el globo pálido lateral. Conclusión. Nuestros datos sugieren que la atorvastatina en el tratamiento posterior a la isquemia ejerce neuroprotección en las zonas exofocales, modulando las poblaciones neuronales gabérgicas y dopaminérgicas del sistema nigroestriatal, lo que podría prevenir trastornos neurológicos.

A Rat Model of Striatonigral Degeneration Generated by Simultaneous Injection of 6-Hydroxydopamine into the Medial Forebrain Bundle and Quinolinic Acid into the Striatum

A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson's disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.

Ketamine alters behavior and decreases BDNF levels in the rat brain as a function of time after drug administration

Objective: To evaluate behavioral changes and brain-derived neurotrophic factor (BDNF) levels in rats subjected to ketamine administration (25 mg/kg) for 7 days. Method: Behavioral evaluation was undertaken at 1 and 6 hours after the last injection. Results: We observed hyperlocomotion 1 hour after the last injection and a decrease in locomotion after 6 hours. Immobility time was decreased and climbing time was increased 6 hours after the last injection. BDNF levels were decreased in the prefrontal cortex and amygdala when rats were killed 6 hours after the last injection, compared to the saline group and to rats killed 1 hour after the last injection. BDNF levels in the striatum were decreased in rats killed 6 hours after the last ketamine injection, and BDNF levels in the hippocampus were decreased in the groups that were killed 1 and 6 hours after the last injection. Conclusion: These results suggest that the effects of ketamine on behavior and BDNF levels are related to the time at which they were evaluated after administration of the drug. .

Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy) in anxiety-like responses in mice

Anxiolytic and anxiogenic-like behavioral outcomes have been reported for methylenedioxymethamphetamine (MDMA or ecstasy) in rodents. In the present experiment, we attempted to identify behavioral, hormonal and neurochemical outcomes of MDMA treatment to clarify its effects on anxiety-related responses in 2-month-old Balb/c male mice (25-35 g; N = 7-10 mice/group). The behavioral tests used were open field, elevated plus maze, hole board, and defensive behavior against predator odor. Moreover, we also determined striatal dopamine and dopamine turnover, and serum corticosterone levels. MDMA was injected ip at 0.2, 1.0, 5.0, 8.0, 10, or 20 mg/kg. MDMA at 10 mg/kg induced the following significant (P < 0.05) effects: a) a dose-dependent increase in the distance traveled and in the time spent moving in the open field; b) decreased exploratory activity in the hole board as measured by number of head dips and time spent in head dipping; c) increased number of open arm entries and increased time spent in open arm exploration in the elevated plus maze; d) increased time spent away from an aversive stimulus and decreased number of risk assessments in an aversive odor chamber; e) increased serum corticosterone levels, and f) increased striatal dopamine level and turnover. Taken together, these data suggest an anxiogenic-like effect of acute MDMA treatment, despite the fact that behavioral anxiety expression was impaired in some of the behavioral tests used as a consequence of the motor stimulating effects of MDMA.

Effect of DHEA on Recovery of Muscle Atrophy Induced by Parkinson's Disease

PURPOSE: The purpose of this study was to determine the effect of dehydroepiandrosterone (DHEA) on recovery of muscle atrophy induced by Parkinson's disease. METHODS: The rat model was established by direct injection of 6-hydroxydopamine (6-OHDA, 20 microg) into the left striatum using stereotaxic surgery. Rats were divided into two groups; the Parkinson's disease group with vehicle treatment (Vehicle; n=12) or DHEA treatment group (DHEA; n=22). DHEA or vehicle was administrated intraperitoneally daily at a dose of 0.34 mmol/kg for 21 days. At 22-days after DHEA treatment, soleus, plantaris, and striatum were dissected. RESULTS: The DHEA group showed significant increase (p<.01) in the number of tyrosine hydroxylase (TH) positive neurons in the lesioned side substantia nigra compared to the vehicle group. Weights and Type I fiber cross-sectional areas of the contralateral soleus of the DHEA group were significantly greater than those of the vehicle group (p=.02, p=.00). Moreover, extracellular signal-regulated kinase (ERK) phosphorylation significantly decreased in the lesioned striatum, but was recovered with DHEA and also in the contralateral soleus muscle, Akt and ERK phosphorylation recovered significantly and the expression level of myosin heavy chain also recovered by DHEA treatment. CONCLUSION: Our results suggest that DHEA treatment recovers Parkinson's disease induced contralateral soleus muscle atrophy through Akt and ERK phosphorylation.

Lack of tolerance for the anti-dyskinetic effects of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, in rats

7-Nitroindazole (7-NI) inhibits neuronal nitric oxide synthase in vivo and reduces l-DOPA-induced dyskinesias in a rat model of parkinsonism. The aim of the present study was to determine if the anti-dyskinetic effect of 7-NI was subject to tolerance after repeated treatment and if this drug could interfere with the priming effect of l-DOPA. Adult male Wistar rats (200-250 g) with unilateral depletion of dopamine in the substantia nigra compacta were treated with l-DOPA (30 mg/kg) for 34 days. On the 1st day, 6 rats received ip saline and 6 received ip 7-NI (30 mg/kg) before l-DOPA. From the 2nd to the 26th day, all rats received l-DOPA daily and, from the 27th to the 34th day, they also received 7-NI before l-DOPA. Animals were evaluated before the drug and 1 h after l-DOPA using an abnormal involuntary movement scale and a stepping test. All rats had a similar initial motor deficit. 7-NI decreased abnormal involuntary movement induced by l-DOPA and the effect was maintained during the experiment before 7-NI, median (interquartile interval), day 26: 16.75 (15.88-17.00); day 28: 0.00 (0.00-9.63); day 29: 13.75 (2.25-15.50); day 30: 0.5 (0.00-6.25); day 31: 4.00 (0.00-7.13), and day 34: 0.5 (0.00-14.63), Friedman followed by Wilcoxon test,vs day 26, P < 0.05;. The response to l-DOPA alone was not modified by the use of 7-NI before the first administration of the drug (l-DOPA vs time interaction, F1,10 = 1.5, NS). The data suggest that tolerance to the anti-dyskinetic effects of a neuronal nitric oxide synthase inhibitor does not develop over a short-term period of repeated administration. These observations open a possible new therapeutic approach to motor complications of chronic l-DOPA therapy in patients with Parkinson’s disease.

Comparative effects of organic and inorganic mercury on in vivo dopamine release in freely moving rats

The present study was carried out in order to compare the effects of administration of organic (methylmercury, MeHg) and inorganic (mercury chloride, HgCl 2 ) forms of mercury on in vivo dopamine (DA) release from rat striatum. Experiments were performed in conscious and freely moving female adult Sprague-Dawley (230-280 g) rats using brain microdialysis coupled to HPLC with electrochemical detection. Perfusion of different concentrations of MeHg or HgCl 2 (2 muL/min for 1 h, N = 5-7/group) into the striatum produced significant increases in the levels of DA. Infusion of 40 muM, 400 muM, or 4 mM MeHg increased DA levels to 907 ± 31, 2324 ± 156, and 9032 ± 70 percent of basal levels, respectively. The same concentrations of HgCl 2 increased DA levels to 1240 ± 66, 2500 ± 424, and 2658 ± 337 percent of basal levels, respectively. These increases were associated with significant decreases in levels of dihydroxyphenylacetic acid and homovallinic acid. Intrastriatal administration of MeHg induced a sharp concentration-dependent increase in DA levels with a peak 30 min after injection, whereas HgCl 2 induced a gradual, lower (for 4 mM) and delayed increase in DA levels (75 min after the beginning of perfusion). Comparing the neurochemical profile of the two mercury derivatives to induce increases in DA levels, we observed that the time-course of these increases induced by both mercurials was different and the effect produced by HgCl 2 was not concentration-dependent (the effect was the same for the concentrations of 400 muM and 4 mM HgCl 2 ). These results indicate that HgCl 2 produces increases in extracellular DA levels by a mechanism differing from that of MeHg.

Neuroprotective effect of BDNF in young and aged 6-OHDA treated rat model of Parkinson disease.

Brain derived neurotrophic factor (BDNF) has been shown to exert trophic effects on dopaminergic neurons against 6-hydroxydopamine (6-OHDA) in young rat. Since the degeneration of substantia nigra dopaminergic neurons that occurs in Parkinson's disease is more often than not confined to elderly individuals, it is of interest to determine whether the effects of BDNF against 6 hydroxydopamine (6-OHDA) in young rats can be extended to aged animals. 6-hydroxydopamine was stereotaxically injected into the striatum of young (3-months) and aged (24-months) rats, which were treated two hours earlier with BDNF. 6-OHDA results in almost complete destruction of substantia nigra pars compacta dopaminergic neurons. BDNF injection significantly changed apomorphine induced rotations from 132 +/- 15 to 181 +/- 10, staircase test from 73 +/- 2% to 61 +/- 3%, initiation time from 7 +/- 2 to 12 +/- 1 sec, and disengage time from 80 +/- 7 to 90 +/- 5 sec in young and aged animals, respectively. It is concluded that BDNF causes the limited behavior recovery of striatal DA systems from 6-OHDA toxicity in aged animals.

Effects of chronic ethanol treatment on monoamine levels in rat hippocampus and striatum

We studied the effects of ethanol on concentrations of noradrenaline (NE), dopamine (DA) and serotonin (5-HT) and their metabolites in rat hippocampus and striatum. Ethanol (2 or 4 g/kg, po, from a 20 percent aqueous solution) was administered daily to male Wistar rats (4-13 per group) for 30 days and animals were sacrificed 30 min or 48 h after the last administration. Monoamines were measured by HPLC and considered significant at P < 0.05. A 47 percent increase in 5-HT levels was observed in the hippocampus with 4 g/kg ethanol in the 30-min protocol. Ethanol (2 and 4 g/kg) decreased DA (2114.5 ± 126.4 and 1785.1 ± 234.2 ng/g wet tissue, respectively) and 3,4-dihydroxyphenylacetic acid (DOPAC, 1477.6 ± 132.1 and 1218.8 ± 271.7 ng/g wet tissue, respectively) levels, while the higher dose also decreased NE (159.8 ± 13.5), 5-HT (228.0 ± 46.8) and 5-hydroxy-3-indoleacetic acid (5-HIAA, 304.4 ± 37.2 ng/g wet tissue), in the striatum after a 48-h withdrawal as compared to controls (DA: 3063.9 ± 321.3; DOPAC: 2379.6 ± 256.0; NE: 292.8 ± 50.2; 5-HT: 412.4 ± 36.2; 5-HIAA: 703.9 ± 61.4 ng/g wet tissue). In the 30-min protocol, ethanol (2 or 4 g/kg) decreased striatal NE (66 and 70 percent) and DA (50 and 36 percent) levels. On the other hand, increases were seen in 5-HIAA (146 and 153 percent) and 5-HT (59 and 86 percent) levels. Ethanol (2 g/kg, po) increased the homovanillic acid (HVA)/DA ratio (129 percent) in the striatum in the 30-min protocol, while at the higher dose it increased the HVA/DA ratio in the 48-h protocol (61 percent). These results indicate alterations in monoamines, mainly in the striatum, after chronic ethanol, which are influenced by dose and by the length of time after the last drug administration.

Histological study of the effect of haloperidol on the corpus striatum of Albino rats and the possible neuro-protective role of vitamin E

Halperidol [HP] is a high potency antipsychotic drug used in treatment of schizophrenia. One of its major side effects is Tardive Dyskinesia [TDD] which is a syndrome of irreversible involuntary movements in tongue, face, arms and legs. Different mechanisms were proposed to explain the pathphysiology of TD and to suggest the proper treatment of this iatrogenic effect caused by HP. The most accepted theory could be histological alterations in the striatum caused by an oxidative stress mechanism and hence the trial of vitamin E [being an antioxidant] as a protective agent against HP-induced TD. The study was performed to investigate the effect of HP on the corpus striatum of rat and the possible neuroprotective role of vitamin E. The present study was carried out on forty adult male albino rats which were divided into four groups; the control group, vitamin E group received only vitamin E orally in a dose of 100 mg/kg/day for 4 consecutive weeks, the HP group received HP in a dose of 40 mg/kg/day for 4 consecutive weeks and the HP and vitamin E group received 100 mg/kg vitamin E in conjunction with HP for the same period. Clinical observation for VCMs [analogue of TD] was made during the period of experiment. At the end of four weeks, animals were sacrificed and brain specimens were prepare for histological study of the basal ganglia by light microscopy using H and E. and DOPA reaction. There were different histological alternations in neurons of the striatum in the HP-treated group, which were in the form of distortion, cellular infiltration,, shrinkage and hypereosinophilia of the cytoplasm. Other neurons showed cytoplasmic vacuolations, Co-administrations of vitamin E, reduced the HP-induced striatal neuronal changes, thus, vitamin E could be of value as a neuroprotective agent against HP-induced striatal changes in humans

Effect of single prenatal haloperidol exposure on hippocampus and striatum of developing rat brain.

Poor development and differentiation of three layered cytoarchitectural pattern of brain, degenerating pyramidal cells with pyknotic nuclei and substantial loss of both large and small pyramidal cells of the hippocampal CA1 region were observed in fetuses of pregnant Charles-Foster rats exposed to single high dose of haloperidol (50 mg/kg body weight) on day 12 of gestation. In treated striatum, reduction in size, complete degeneration of multipolar cells with fragmented nuclei and increased extracellular spaces were observed. Unsacrificed group of day 12 haloperidol treated rat offsprings at 9 weeks of age exhibited cognitive behavioural dysfunctions in passive avoidance (behaviour) test. These findings indicate that a single (high dose) prenatal haloperidol exposure during critical period of CNS development not only induces micromorphological aberrations in foetal hippocampus and striatum but also lasting cognitive impairment in adult rat offsprings.

Selective destruction of nigrostriatal dopaminergic neurons does not alter [3H]-ryanodine binding in rat striatum

Dopamine nigrostriatal neurons are important for motor control and may contain a particularly dense population of ryanodine receptors involved in the control of dopamine release. To test this hypothesis, we used a classical model of unilateral selective lesion of these neurons in rats based on 6-hydroxydopamine (6-OHDA) injection into the substantia nigra. Binding of [3H]-GBR 12935, used as a presynaptic marker since it labels specifically the dopamine uptake complex, was dramatically decreased by 83-100 percent in striatum homogenates after 6-OHDA lesion. On the contrary, no reduction of [3H]-ryanodine binding was observed. The present data indicate that [3H]-ryanodine binding sites present in rat striatum are not preferentially localized in dopaminergic terminals

Effects of flunarizine on dopamine dependent behaviours in rats.

1. Radio-ligand binding study has demonstrated that flunarizine has a high affinity for the rat striatal D 2 dopamine (DA) receptors. 2. In the present behavioural study conducted in rats it was observed that flunarizine, unlike the postsynaptic striatal D 2 DA receptor agonist apomorphine, did not induce stereotyped behaviour (SB) in rats. This indicates that flunarizine does not act as an agonist at the postsynaptic striatal D 2 DA receptors. 3. Flunarizine however, like the postsynaptic striatal D 2 DA receptor antagonist haloperiodal, inhibited the conditioned avoidance response, induced catalepsy and antagonized the SB induced by the DA agonists apomorphine and methamphetamine. 4. Our findings indicate that flunarizine acts as a postsynaptic striatal D 2 DA receptor antagonist.

Evidence of interaction between fluoxetine and isosorbide dinitrate on neuroleptic-induced catalepsy in mice

Drugs which influence 5-HTergic mechanisms can modify neuroleptic-induced catalepsy (NC) in rodents, a phenomenon produced by striatal dopamine (DA) receptor blockade. Previous research also suggests a role for endogenous nitric oxide (NO) in the modulation of striatal DAergic neurotransmission; in addition, NO seems to play a role in the 5-HT reuptake mechanism. It is known that clomipramine potentiates NC in mice, but the reported effects of selective 5-HT reuptake inhibitors(SSRIs) in this model are rather contradictory. We then decided to re-address this issue, investigating the effect of fluoxetine (FX), an SSRI, on NC. In view of the ubiquitous role of NO as a central neuromodulator, we also studied the effect of isosorbide dinitrate (ID), a centrally active NO donor, and how both drugs interact to effect the phenomenon of NC. Catalepsy was induced in male albino mice with haloperidol (H; 1 mg/kg, ip) and measured at 30-min interval by means of a bar test. Drugs (FX, ID and FX + ID) or saline (controls) were injected ip 30 min before H, with each animal used only once. FX (5 mg/kg) significantly reduced NC, with maximal attenuation (about 74 percent) occurring at 150 min after H. ID (5 mg/kg) also inhibited NC (150 min: 62 percent attenuation). The combined drugs (FX + ID group), however caused a great potentiation of NC (4.7-fold at its maximum, at 90 min). The effect observed with ID is compatible with the hypothesis that NO increases DA release in the striatum. The attenuation of NC observed with FX may be due to a preferential net effect oon the raphe somatodendritic synapse, where inhibitory 5-HT(1A) autoreceptors are operative. The enhancement of NC caused by combined administration of FX and ID suggests the presence of a pharmacodynamic interaction, whose mechanism, still unclear, may be related to a decrease in striatal DA release.

Changes in transition metal contents in rat brain regions after in vivo quinolinate intrastriatal administration

Total copper and manganese contents were measured in five rat brain regions 7 days after a unilateral striatal injection of quinolinic acid (QUIN, 240 nmol/1µl), an endogenous N-methyl-D-aspartate (NMDA) receptor agonist. Concentrations of both transition metals were evaluated in tissue of brain cortex, hippocampus, corpus striatum, midbrain and cerebellum of saline- and QUIN-treated rats using graphite furnace atomic absorption spectrophotometry. Increases in copper content were observad after QUIN striatal injection in cerebellum, hippocampus, midbrain and corpus striatum (37, 55, 71 and 152 percent as compared against control values, respectively) but not in brain cortex. Manganese levels were found enhanced only in corpus striatum of QUIN-treated rats by 35 percent vs. control values, but not in all other brain regions analyzed. QUIN-induced increases in regional copper content were partially prevented in hippocampus, midbrain and striatum (17, 57, and 23 percent vs. control, respectively) by pretreatment of rats with an NMDA receptor antagonist, dizocilpine (MK-801, 10 mg/kg, i.p.), administered 60 min before QUIN microinjection. The same protective effect of fizocilpine was observed against QUIN-induced enhancement of striatal manganese content (-0.45 percent vs. control). These findings resemble those changes observed in postmortem Huntington's disease brain and suggest that alterations in regional content of copper, but not in manganese, may be a consequence of the spreading of QUIN-induced neurotoxic events into the striatal tissue to the neighboring regions of the brain, by action of QUIN on NMDA receptors

Mazindol: efeitos anorético e neurotóxico em ratos jovens e idosos / Mazindol: anoretic and neurotoxic effects in young old rats

Os efeitos da administraçäo crônica do mazindol (5 e 10 mg/kg i.p. e 60 mg/kg s.c) sobre a evoluçäo ponderal e a atividade da tirosina hidroxilase cerebral foram determinados em ratos machos jovens e idosos. O potencial anorético da droga foi observado através da avaliaçäo comparativa do peso corporal dos animais. A atividade da tirosina hidroxilase no estriato foi utilizada como parâmetro indireto da possível neurotoxicidade do mazindol. Nos ratos jovens notou-se uma perda significativa de peso aos 15 dias de tratamento, com recuperaçäo ascendente deste ao longo do tempo. Nos ratos idosos houve também perda de peso significativa; no entanto, tal recuperaçäo näo foi observada. Näo foram detectadas alteraçöes significativas da atividade enzimática em relaçäo aos grupos controles para ambas as idades. Estes resultados säo analisados a partir de dados encontrados na literatura