Biomedical subjects

R Frussa-Filho

Publications and source records attributed to R Frussa-Filho.

At least 19 recordsLinked to original sources

PubMed2006

Drug-induced home cage conspecifics' behavior can potentiate behavioral sensitization in mice.

The effect of home cage conspecifics' behavior on locomotor sensitization to amphetamine (AMP) or ethanol (ETOH) were investigated. Female mice were repeatedly treated with saline or AMP (2.0 mg/kg for 13 days--Experiment 1) or saline or ETOH (1.8 g/kg for 21 days--Experiment 2) in home cages where all the animals had the same treatment (homogeneous home cages--HOM-HC) or in home cages where half of the animals were drug-treated and half of them were saline-treated (heterogeneous home cages--HET-HC). Behavioral sensitization was evaluated by the quantification of open-field locomotor activity after AMP or ETOH challenge injection, respectively. In both experiments, behavioral sensitization was potentiated in HOM-HC maintained animals. These results suggest that the behavioral sensitization phenomenon can be modified by home cage conspecifics' behavior.

Amphetamine↗

PubMed2006

Association of paradoxical sleep deprivation and ecstasy (MDMA) enhances genital reflexes in male rats.

Ecstasy ((+/-)3,4-methylenedioxymethamphetamine, MDMA) is a psychostimulant and a synthetic derivative of amphetamine that, according to its consumers, promotes the enhancement of sexual pleasure. This study sought to investigate the effects of ecstasy in the genital reflexes of paradoxical sleep deprived (PSD) male rats. Distinct groups of PSD rats were administered with saline or different doses of ecstasy. The incidence of genital reflexes was verified for 100 min. The four doses that were used induced genital reflexes in PSD animals and these significantly differed from their respective treated control groups. Under the influence of two intermediary doses (2.5 and 5mg/kg), all animals displayed erection and ejaculation. The frequency of genital reflexes was also significantly greater than in relation to the PSD-saline group. The comparison between cocaine and ecstasy in PSD rats revealed that ecstasy induced more erections and ejaculations than cocaine. Thus, the present results showed a great enhancement of the genital reflexes of PSD rats that might have occurred due to serotoninergic alterations induced by this illicit substance when associated to sleep deprivation.

Adrenergic Uptake Inhibitors↗

PubMed2005

Effects of morphine on the plus-maze discriminative avoidance task: role of state-dependent learning.

RATIONALE: The amnesic effects of morphine may be related to its action on nociception, anxiety, or locomotion. This effect is also suggested to be related to state dependency. OBJECTIVES: The aims of this study were to verify the effects of morphine on mice tested in the plus-maze discriminative avoidance task (DAT) that uses light and noise as aversive stimuli and allows the concomitant evaluation of learning, memory, anxiety, and locomotion and also to verify the possible role of state-dependent learning in the effects of morphine. METHODS AND RESULTS: The DAT was conducted in a modified elevated plus-maze. In the training, the aversive stimuli were applied when mice entered in one of the enclosed arms, whereas in the test, no stimuli were applied. The main results showed that (1) pretraining morphine (5-20 mg/kg i.p.) induced retrieval deficits (evaluated by the time spent in the aversive arm in the test) but not acquisition deficits (evaluated by the decrease in aversive arm exploration along the training); (2) pretest morphine (5-10 but not 20 mg/kg) counteracted this deficit; (3) morphine induced hypolocomotion (decreased number of entries in the arms), irrespective of memory alterations; and (4) morphine did not alter anxiety-like behavior (evaluated by the time spent in the open arms) during the training. CONCLUSIONS: Morphine given before training induces retrieval deficits in mice tested in the DAT, and these deficits could be related to morphine-induced state-dependent learning. Neither the memory deficit induced by pretraining morphine nor the reversal of this deficit by pretest morphine seems to be related to anxiety levels or locomotor alterations.

Animals↗

PubMed2005

Effects of long-term continuous exposure to light on memory and anxiety in mice.

The studies on the relationship between the light/dark cycle and memory function mostly used protocols of acute disruption of the circadian rhythm. The aim of the present study is to verify the effects of long-term continuous exposure to light on memory, anxiety and motor parameters of mice tested in the plus-maze discriminative avoidance task. Mice were conditioned to choose between the two enclosed arms (one aversive and one non-aversive) while avoiding the open arms of a modified elevated plus-maze apparatus. Memory was evaluated by the time spent in the aversive enclosed arm, anxiety was evaluated by the time spent in the open arms and locomotor behavior was evaluated by number of entries in the arms of the maze. The results showed that long-term (35-42 days) continuous light exposure did not modify memory or anxiety parameters but increased locomotor activity. While the increase in locomotor behavior is in line with previous studies, the unexpected absence of alterations in memory and anxiety (reported to be influenced by the circadian rhythm) is discussed.

Analysis of Variance↗

PubMed2005

Effects of social isolation on aging-induced orofacial movements in rats.

World population is becoming older, and aging is a common risk factor for a number of pathologies. In this respect, it is important to study possible factors that could modify alterations implicated in the process of aging. The aim of the present study is to verify the effects of social isolation on the expression of orofacial movements in adult and old rats. Adult and old rats were housed isolated for 5 days or kept in their home cages in groups of six. Before and after this period, orofacial movements and open-field general activity were evaluated. Aging-induced orofacial movements were abolished by isolation. On the other hand, isolated adult rats presented an increase in orofacial movements. General activity was decreased by aging but was not modified by isolation. Our results indicate that social isolation produces different effects in adult and old rats, and these effects are specific for orofacial movements and not related to a decrease in general motor activity.

Aging↗

PubMed2005

Role of learning of open arm avoidance in the phenomenon of one-trial tolerance to the anxiolytic effect of chlordiazepoxide in mice.

A single exposure to the elevated plus-maze (EPM) test of anxiety reduces or abolishes the anxiolytic efficacy of benzodiazepines on a second trial. Some possible explanations to the occurrence of this phenomenon (one-trial tolerance-OTT) involve behavioral modifications thought to be consequence of some kind of learning in the first trial. In the present study, the influence of learning-impairing situations on the effects of the benzodiazepine chlordiazepoxide on mice re-tested in the EPM is investigated. The results showed that: (1) as expected, the administration of chlordiazepoxide to mice re-tested in the EPM- under the same conditions of the first trial- failed to induce anxiolysis; (2) a decreased percent time in the open arms was observed on the second trial of mice exposed to both trials under the same experimental conditions; (3) neither the increase in open arm avoidance by mice re-exposed to the EPM nor the OTT to chlordiazepoxide effect were modified by administration of the amnestic agent scopolamine; (4) the decrement of the duration of the first trial to 1 min or the change in light and noise conditions in both trials counteracted the increase in open arm avoidance on trial 2; (5) none of the later procedures modified the phenomenon of OTT. Although not discarding the modulation exerted by other memory processes in the OTT phenomenon, the results indicate that situations that impair the learned avoidance response to the open arms in the EPM do not modify the phenomenon of OTT.

Animals↗

PubMed2004

Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice.

Numerous animal and clinical studies have described memory deficits following sleep deprivation. There is also evidence that the absence of sleep increases brain oxidative stress. The present study investigates the role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Mice were sleep deprived for 72 h by the multiple platform method-groups of 4-6 animals were placed in water tanks, containing 12 platforms (3 cm in diameter) surrounded by water up to 1 cm beneath the surface. Mice kept in their home cage or placed onto larger platforms were used as control groups. The results showed that hippocampal oxidized/reduced glutathione ratio as well as lipid peroxidation of sleep-deprived mice was significantly increased compared to control groups. The same procedure of sleep deprivation led to a passive avoidance retention deficit. Both passive avoidance retention deficit and increased hippocampal lipid peroxidation were prevented by repeated treatment (15 consecutive days, i.p.) with the antioxidant agents melatonin (5 mg/kg), N-tert-butyl-alpha-phenylnitrone (200 mg/kg) or vitamin E (40 mg/kg). The results indicate an important role of hippocampal oxidative stress in passive avoidance memory deficits induced by sleep deprivation in mice.

Animals↗

PubMed2004

Important role of striatal catalase in aging- and reserpine-induced oral dyskinesia.

Tardive dyskinesia, the most serious iatrogenic movement disorder, has been tentatively associated with nigrostriatal dopaminergic supersensitivity and with oxidative stress. It is also suggested that long-term neuroleptic treatment does not cause oral dyskinesia (OD), but interacts with some substrate of brain aging, resulting in the premature emergence of OD, that can occur spontaneously with aging. In order to investigate a possible role of nigrostriatal dopaminergic supersensitivity and of oxidative stress in aging- and reserpine-induced OD, the stereotyped behavior induced by dopaminergic agonists, a functional index of dopaminergic striatal activity, as well as the striatal antioxidant enzymes glutathione peroxidase and catalase were assessed. We demonstrate that, opposite to normotensive Wistar rats (NWR), spontaneously hypertensive rats (SHR) do not develop aging- or reserpine-OD. There were no differences between NWR and SHR in stereotyped behavior or in striatal glutathione peroxidase activity. Adult and old SHR presented higher striatal catalase activity relative to NWR, and aging increased it only in SHR. The catalase inhibitor aminotriazole reverted the absence of aging- and reserpine-induced OD in SHR. Our results suggest an important role of striatal catalase in the development of reserpine- and aging-induced OD.

Aging↗

PubMed2004

Effects of pre- or post-training paradoxical sleep deprivation on two animal models of learning and memory in mice.

The aim of the present study was to verify the effects of pre- or post-training paradoxical sleep (PS) deprivation in mice tested in the passive and the plus-maze discriminative avoidance tasks. Three-month-old Swiss male mice were placed in narrow platforms in a water tank for 72 h to prevent the occurrence of PS. Control animals were kept in the same room, but in their home cages. Before or after this period, the animals were submitted to the training session of one of the behavioral tasks. The test sessions were performed 3 and 10 days after the training. The animals that were PS-deprived before the training session showed retention deficits in the test sessions performed 3 days later in both tasks (decreased latency to enter the dark chamber of the passive avoidance apparatus or increased percent time spent in the aversive arm of the plus-maze discriminative avoidance apparatus). Animals that were PS deprived after the training session showed no differences from control animals in the test sessions performed 3 days after the training in any of the tasks, but showed passive and discriminative avoidance retention deficits in the test performed 10 days after the training. The results suggest that both pre- and post-training paradoxical sleep deprivation produce memory deficits in mice. However, these effects have different temporal characteristics.

Animals↗

PubMed2004

Effects of morphine or naloxone on cocaine-induced genital reflexes in paradoxical sleep-deprived rats.

The involvement of opioidergic neurotransmission in the modulation of genital reflexes induced by paradoxical sleep deprivation (PSD) and cocaine in rats was the aim of the present study. Morphine (0, 1, 5 and 10 mg/kg) and naloxone (0, 0.3, 3 and 30 mg/kg) were administered prior to saline or cocaine to rats that had been deprived of sleep and the incidence of penile erections (PE) and ejaculations (EJ) was measured. PSD alone induced PE in 50% and EJ in 20% of the rats, but these behaviors were not influenced by morphine or naloxone. Cocaine potentiated the incidence of genital reflexes in PSD rats to 90% (PE) and 70% (EJ). Morphine and not naloxone significantly reduced the percentage of rats displaying this response at the highest doses. Morphine also significantly reduced PE and EJ frequencies at 10 mg/kg. Furthermore, this inhibitory effect of morphine on genital reflexes was prevented by the prior injection of naloxone. Although a number of factors are involved in such a complex phenomenon as PE and EJ, our data show that activation of the opioidergic systems by the agonist morphine reduces genital reflexes-induced by cocaine in PSD males while the antagonist, naloxone, did not have any significant effect. The findings suggest that the stimulating effects of cocaine in potentiating genital reflexes in PSD rats can be unidirectionally modified by opioidergic systems.

Animals↗

PubMed2004

Monosialoganglioside (GM1) attenuates the behavioural effects of long-term haloperidol administration in supersensitive rats.

In the present study we investigated the effects of co-administration of GM(1) (15.0 mg/kg, twice daily, for 30 days) and haloperidol (1.0 mg/kg, twice daily, for 30 days), as well as the effects of a 5-day treatment with this dose of GM(1) after withdrawal from haloperidol in rats. The animals were evaluated in the open-field test and apomorphine-induced stereotyped behaviour. The results show that GM(1) was able to attenuate dopaminergic supersensitivity evaluated by the locomotion frequency at 24 and 48 h after the withdrawal from haloperidol. On the other hand, rearing frequency was changed neither by haloperidol nor by GM(1.) In haloperidol-treated rats immobility time differs from 30 min observation session in comparison with the following sessions after the withdrawal from neuroleptic. Apomorphine-induced stereotyped behaviour produced a significant increase in scores of haloperidol-withdrawn rats. GM(1) did not modify the haloperidol effects and did not change the dopamine receptor affinity to apomorphine 100 h from abrupt neuroleptic withdrawal.

Analysis of Variance↗

PubMed2004

Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid.

Intracellular calcium homeostasis is important for cell survival. However, increase in mitochondrial calcium (Ca2+m) induces opening of permeability transition pore (PTP), mitochondrial dysfunction and apoptosis. Since alterations of intracellular Ca2+ and reactive oxygen species (ROS) generation are involved in cell death, they might be involved in neurodegenerative processes such as Huntington's disease (HD). HD is characterized by the inhibition of complex II of respiratory chain and increase in ROS production. In this report, we studied the correlation between the inhibitor of the complex II, 3-nitropropionic acid (3NP), Ca2+ metabolism, apoptosis and behavioural alterations. We showed that 3NP (1 mm) is able to release Ca2+m, as neither Thapsigargin (TAP, 2 microm) nor free-calcium medium affected its effect. PTP inhibitors and antioxidants inhibited this process, suggesting an increase in ROS generation and PTP opening. In addition, 3NP (0.1 mm) also induces apoptotic cell death. Behavioural changes in animals treated with 3NP (20 mg/kg/day for 4 days) were also attenuated by pre- and co-treatment with vitamin E (VE, 20 mg/kg/day). Taken together, our results show that complex II inhibition could involve Ca2+m release, oxidative stress and cell death that may precede motor alterations in neurodegenerative processes such as HD.

Animals↗

PubMed2004

Role of anxiety levels in memory performance of spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) show behavioural differences when compared to their strain-matched controls. These differences include decreased anxiety-like behaviour in SHR, while both improved performance and behavioural deficits have been reported in learning/memory studies. Considering that alterations in anxiety levels during the training session can modify retention performance in animal models of memory, the aim of the present study was to investigate the role of anxiety levels in the performance of SHR rats in the plus-maze discriminative avoidance task (PM-DAT), in which memory and anxiety are evaluated simultaneously. Adult (5-month-old) and young (45-day-old) SHR and normotensive Wistar rats (NWR) were treated with chlordiazepoxide (CDZ) or saline. Thirty minutes later, rats were submitted to the PM-DAT training session. After 24 h, the test session was performed. The results showed that: (1) adult SHR showed lower anxiety levels compared to adult NWR; (2) adult SHR and NWR, as well as young NWR, showed significant retention of the task, while young SHR showed impaired performance; (3) 5.0 mg/kg CDZ decreased anxiety levels in adult NWR and young and adult SHR; (4) 5.0 mg/kg CDZ impaired retention in adult SHR and NWR and increased retention in young SHR. Our data suggest an important role of anxiety levels in the performance of SHR in a plus-maze discriminative avoidance task.

Animals↗

PubMed2003

Antidyskinetic effects of risperidone on animal models of tardive dyskinesia in mice.

The effects of risperidone, an atypical neuroleptic, were investigated on two animal models of tardive dyskinesia (TD). The repeated administration of reserpine (1.0mg/kg) or haloperidol (2.0mg/kg) induces orofacial movements in mice, which are very similar to those observed in humans presenting TD. The effects of acute or repeated treatment with several doses of risperidone (0.1; 0.5; 2.0 or 4.0) on the expression and development of orofacial movements in reserpine- and haloperidol-treated male mice were investigated. The results showed that risperidone per se did not induce the development of orofacial movements. In addition, this drug was able to attenuate the expression and the development of reserpine-as well as haloperidol-induced orofacial movements. These results are in line with several clinical studies that suggest not only a lower incidence of TD in schizophrenic patients treated with risperidone, but also an antidyskinetic effect of this drug in patients previously treated with classical neuroleptics.

Administration, Oral↗

PubMed2002

One-trial tolerance to the effects of chlordiazepoxide in the elevated plus-maze is not due to acquisition of a phobic avoidance of open arms during initial exposure.

A single exposure to the elevated plus-maze (EPM) test of anxiety reduces or abolishes the anxiolytic-like efficacy of benzodiazepines. This phenomenon called one-trial tolerance has been suggested to represent the acquisition of a phobic-like response to the open arms during trial 1. The present study was designed to examine the effects of chlordiazepoxide (5 mg/kg, ip) on the behaviour of rats in a conventional EPM apparatus after previous exposure to a four-open-arm EPM, a four-enclosed arm EPM or a conventional EPM, as well as in naive rats. Chlordiazepoxide had clear-cut anxiolytic-like effects (increased percentage of time spent on the open arms) in a traditional EPM in naive rats and in animals previously exposed to a four-open-arm EPM. However, it was ineffective in rats previously exposed to a traditional or a four-closed-arm EPM. Thus, the phenomenon of one-trial tolerance does not depend upon initial open-arm experience.

Analysis of Variance↗

PubMed2002

Effects of melatonin on orofacial movements in rats.

RATIONALE: While reserpine-induced oral movements (OM), an animal model of tardive dyskinesia, are more persistent in old than in adult rats, old animals present spontaneous OM, which are phenomenologically similar to those presented by reserpine-treated adult rats. We postulate that these OM may be the result of oxidative stress induced by both age and reserpine treatment. OBJECTIVES: We intended to determine the preventative effects of exogenous melatonin (one of the most important endogenous antioxidants) as well as suppression of endogenous melatonin via continuous exposure to light on reserpine- or age-induced OM in rats. METHODS: Adult (4 months of age) male Wistar rats were repeatedly treated with saline or melatonin (5 mg/kg, IP) and saline or reserpine and kept under a 12-h light/dark cycle for quantification of reserpine-induced OM as well as oxidative stress (via quantification of lipid peroxidation). To verify the effects of endogenous melatonin suppression on reserpine-induced OM, adult rats were repeatedly treated with saline or reserpine and continuously exposed to light. To verify the effects of exogenous melatonin on age-induced OM older (20 months of age) rats were long-term treated with saline or melatonin and kept under a 12-h light/dark cycle. RESULTS: Melatonin attenuated both reserpine- and age-induced OM. Reserpine enhanced striatal lipid peroxidation, that was prevented by melatonin co-administration. Continuous exposure to light increased spontaneous as well as reserpine-induced OM, indicating that endogenous melatonin may be involved in this movement disorder. CONCLUSIONS: We suggested that melatonin attenuates both reserpine- and age-induced OM in rats.

Age Factors↗

PubMed2002

Acute buspirone abolishes the expression of behavioral dopaminergic supersensitivity in mice.

Previous studies have shown that rats withdrawn from long-term treatment with dopamine receptor blockers exhibit dopaminergic supersensitivity, which can be behaviorally evaluated by enhanced general activity observed in an open-field. Recently, it has been reported that co-treatment with the non-benzodiazepine anxiolytic buspirone attenuates the development of haloperidol-induced dopaminergic supersensitivity measured by open-field behavior of rats. The aims of the present study were: 1) to determine, as previously reported for rats, if mice withdrawn from long-term neuroleptic treatment would also develop dopaminergic supersensitivity using open-field behavior as an experimental paradigm, and 2) to examine if acute buspirone administration would attenuate the expression of this behavioral dopaminergic supersensitivity. Withdrawal from long-term haloperidol treatment (2.5 mg/kg, once daily, for 20 days) induced a significant (30%) increase in ambulation frequency (i.e., number of squares crossed in 5-min observation sessions) but did not modify rearing frequency or immobility duration in 3-month-old EPM-M1 male mice observed in the open-field apparatus. Acute intraperitoneal injection of buspirone (3.0 and 10 but not 1.0 mg/kg, 12-13 animals per group) 30 min before open-field exposure abolished the increase in locomotion frequency induced by haloperidol withdrawal. These data suggest that the open-field behavior of mice can be used to detect dopaminergic supersensitivity, whose expression is abolished by acute buspirone administration.

Animals↗

PubMed2001

Effects of amphetamine on the plus-maze discriminative avoidance task in mice.

RATIONALE: The contradictory amphetamine effects on memory could be due to different protocols of amphetamine administration or the well-known anxiogenic effect of the drug. OBJECTIVE: The effects of different protocols of administration of amphetamine were investigated on mice tested in the plus-maze discriminative avoidance task (DAT), which provides simultaneous information about memory and anxiety. METHODS: Acutely pre- or post-training, 0.3, 1.0, or 3.0 mg/kg amphetamine-treated, 10-day chronically 3.0 mg/kg amphetamine-treated, 0.3 mg/kg amphetamine plus 0.25 mg/kg scopolamine and 3.0 mg/kg amphetamine plus 3.0 mg/kg tacrine-treated mice were conditioned to choose between two enclosed arms (one of which was aversive) while avoiding two open arms. Learning/memory was evaluated by the percentage time in the aversive enclosed arm (PTAV), and anxiety by the percentage time in the open arms (PTO). RESULTS: Given acutely before conditioning, amphetamine significantly decreased PTO in training, suggesting an anxiogenic effect, and significantly increased PTAV in the test, suggesting an amnestic action. Given acutely after the conditioning, no action of this drug on memory was found. After repeated treatment, the anxiogenic effect disappeared, while the amnestic effect remained. While no effects of subeffective doses of amphetamine and scopolamine co-administration were detected, tacrine attenuated the amnestic effect of amphetamine. CONCLUSIONS: Amphetamine has different effects on DAT when given pre- or post-training. While acute pre-training amnestic action is temporally correlated with an anxiogenic effect, there is tolerance to the anxiogenic but not to the amnestic effect after repeated administration. Because this acute amnestic effect of amphetamine is attenuated by tacrine, a possible relationship with cholinergic system cannot be discarded as a mechanism to amphetamine-induced amnesia in DAT.

Amphetamine↗