Effects of Toluene on the Development of the Inner Ear and Lateral Line Sensory System of Zebrafish / 生物医学与环境科学（英文）

Objective@#The aim of this study was to explore the ototoxicity of toluene in the early development of zebrafish embryos/larvae.@*Methods@#Zebrafish were utilized to explore the ototoxicity of toluene. Locomotion analysis, immunofluorescence, and qPCR were used to understand the phenotypes and molecular mechanisms of toluene ototoxicity.@*Results@#The results demonstrated that at 2 mmol/L, toluene induced zebrafish larvae death at 120 hours post fertilization (hpf) at a rate of 25.79% and inhibited the rate of hatching at 72 hpf. Furthermore, toluene exposure inhibited the distance travelled and average swimming velocity of zebrafish larvae while increasing the frequency of movements. As shown by fluorescence staining of hair cells, toluene inhibited the formation of lateral line neuromasts and middle line 1 (Ml @*Conclusion@#This study indicated that toluene may affect the development of both the inner ear and lateral line systems in zebrafish, while the lateral line system may be more sensitive to toluene than the inner ear.

Melatonin decreases cocaine-induced locomotor activity in pinealectomized rats

Objective: Several studies have shown that the time of day regulates the reinforcing effects of cocaine. Additionally, melatonin and its MT1 and MT2 receptors have been found to participate in modulation of the reinforcing effects of such addictive drugs as cocaine. Loss of the diurnal variation in cocaine-induced locomotor sensitization and cocaine-induced place preference has been identified in pinealectomized mice. In addition, several studies in rodents have shown that administration of melatonin decreased the reinforcing effects of cocaine. The objective of this study was to evaluate the effect of melatonin on cocaine-induced locomotor activity in pinealectomized rats at different times of day (zeitgeber time [ZT]4, ZT10, ZT16, and ZT22). Methods: Naïve, pinealectomized Wistar rats received cocaine at different times of day. Melatonin was administered 30 min before cocaine; luzindole was administered 15 min prior to melatonin and 45 min before cocaine. After administration of each treatment, locomotor activity for each animal was recorded for a total of 30 min. Pinealectomy was confirmed at the end of the experiment through melatonin quantitation by ELISA. Results: Cocaine-induced locomotor activity varied according to the time of day. Continuous lighting and pinealectomy increased cocaine-induced locomotor activity. Melatonin administration decreased cocaine-induced locomotor activity in naïve and pinealectomized rats at different times of day. Luzindole blocked the melatonin-induced reduction in cocaine-induced locomotor activity in pinealectomized rats. Conclusion: Given its ability to mitigate various reinforcing effects of cocaine, melatonin could be a useful therapy for cocaine abuse.

Effects of lithium on inflammatory and neurotrophic factors after an immune challenge in a lisdexamfetamine animal model of mania

Objective: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. Methods: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. Results: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. Conclusion: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.

Coumarin analogue 3-methyl-7H-furo[3,2-g]chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

Hypericum perforatum chronic treatment affects cognitive parameters and brain neurotrophic factor levels

Objective: To evaluate the effects of Hypericum perforatum (hypericum) on cognitive behavior and neurotrophic factor levels in the brain of male and female rats. Methods: Male and female Wistar rats were treated with hypericum or water during 28 days by gavage. The animals were then subjected to the open-field test, novel object recognition and step-down inhibitory avoidance test. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) levels were evaluated in the hippocampus and frontal cortex. Results: Hypericum impaired the acquisition of short- and long-term aversive memory in male rats, evaluated in the inhibitory avoidance test. Female rats had no immediate memory acquisition and decreased short-term memory acquisition in the inhibitory avoidance test. Hypericum also decreased the recognition index of male rats in the object recognition test. Female rats did not recognize the new object in either the short-term or the long-term memory tasks. Hypericum decreased BDNF in the hippocampus of male and female rats. Hypericum also decreased NGF in the hippocampus of female rats. Conclusions: The long-term administration of hypericum appears to cause significant cognitive impairment in rats, possibly through a reduction in the levels of neurotrophic factors. This effect was more expressive in females than in males.

Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats

The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS) and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days). After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip) and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.

Chronic dosing with mirtazapine does not produce sedation in rats

Objective: Sedation/somnolence are major side effects of pharmacotherapies for depression, and negatively affect long-term treatment compliance in depressed patients. Use of mirtazapine (MIR), an atypical antidepressant approved for the treatment of moderate to severe depression with comorbid anxiety disorders, is associated with significant sedation/somnolence, especially in short-term therapy. Nonetheless, studies with human subjects suggest that MIR-induced sedation is transient, especially when high and repeated doses are used. The purpose of this study was to explore the effects of acute and chronic administration of different doses of MIR on sedation in the rat. Methods: Assessment of sedation was carried out behaviorally using the rotarod, spontaneous locomotor activity, and fixed-bar tests. Results: A 15-mg/kg dose of MIR induced sedative effects for up to 60 minutes, whereas 30 mg/kg or more produced sedation within minutes and only in the first few days of administration. Conclusion: These results suggest that 30 mg/kg is a safe, well-tolerated dose of MIR which generates only temporary sedative effects.

Selenocysteine modulates resistance to environmental stress and confers anti-aging effects in C. elegans

OBJECTIVE: The free radical theory of aging suggests that cellular oxidative damage caused by free radicals is a leading cause of aging. In the present study, we examined the effects of a well-known anti-oxidant amino acid derivative, selenocysteine, in response to environmental stress and aging using Caenorhabditis elegans as a model system. METHOD: The response to oxidative stress induced by H2O2 or ultraviolet irradiation was compared between the untreated control and selenocysteine-treated groups. The effect of selenocysteine on lifespan and fertility was then determined. To examine the effect of selenocysteine on muscle aging, we monitored the change in motility with aging in both the untreated control and selenocysteine-treated groups. RESULTS: Dietary supplementation with selenocysteine significantly increased resistance to oxidative stress. Survival after ultraviolet irradiation was also increased by supplementation with selenocysteine. Treatment with selenocysteine confers a longevity phenotype without an accompanying reduction in fertility, which is frequently observed in lifespan-extending interventions as a trade-off in C. elegans. In addition, the age-related decline in motility was significantly delayed by supplementation of selenocysteine. CONCLUSION: These findings suggest that dietary supplementation of selenocysteine can modulate response to stressors and lead to lifespan extension, thus supporting the free radical theory of aging.

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.

The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose / Efeitos da administração intracerebroventricular de rocurônio sobre o sistema nervoso central de ratos e determinação da dose indutora de crise epiléptica

Abstract Background: The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. Methods: A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n = 6), Group 1/10 (n = 6), and Group 1/100 (n = 6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. Results: The rocuronium bromide seizure threshold value was found to be 0.056 ± 0.009 µmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286 µmoL/kg-1. A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. Conclusions: This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures.

Resumo Justificativa: O objetivo deste estudo foi investigar os efeitos do brometo de rocurônio administrado intracerebroventricularmente sobre o sistema nervoso central, determinar a dose do limiar convulsivo de rocurônio em ratos e investigar os efeitos de rocurônio no sistema nervoso central em diluições de 1/5, 1/10 e 1/100 da dose do limiar convulsivo determinada. Métodos: Uma cânula permanente foi colocada no ventrículo lateral do cérebro dos animais. O estudo foi projetado em duas fases. Na primeira, a dose do limiar convulsivo do brometo de rocurônio foi determinada. Na segunda, o Grupo R 1/5 (n = 6), o Grupo 1/10 (n = 6) e Grupo 1/100 (n = 6) foram formados com doses de 1/5, 1/10 e 1/100, respectivamente, da dose do limiar convulsivo de brometo de rocurônio obtida. Resultados: Descobrimos que o valor do limiar convulsivo de brometo de rocurônio é 0,056 ± 0,009 µmoL. O limiar convulsivo, como uma função do peso corporal dos ratos, foi calculado como 0,286 µmoL/kg-1. Uma dose de 1/5 da dose do limiar convulsivo causou principalmente abertura postural dos membros e tremores em todo o corpo, enquanto uma dose de 1/10 da dose do limiar convulsivo causou agitação e tremores. Uma dose de 1/100 da dose do limiar convulsivo foi associada à diminuição da atividade locomotora. Conclusões: Este estudo mostrou que o brometo de rocurônio tem efeitos deletérios relacionados com a dose sobre o sistema nervoso central e pode produzir efeitos excitatórios dependentes da dose e convulsões.

Chronic intermittent exposure to ayahuasca during aging does not affect memory in mice

The Quechua term ayahuasca refers to a beverage obtained from decoctions of the liana Banisteriopsis caapi with leaves of Psychotria viridis. The ritualistic use of ayahuasca is becoming a global phenomenon, with some individuals using this beverage throughout life, including in old age. Cognitive impairment is a common manifestation during aging. There are conflicting reports on the ability of some ayahuasca compounds to exert neuroprotective or neurotoxic effects that could improve or impair learning and memory. Animal models provide a relevant and accessible means of investigating the behavioral effects of ayahuasca without the environmental conditions associated with the ritualistic use of the beverage. In this study, we investigated the influence of chronic ayahuasca exposure throughout aging on the spatial reference and habituation memories of mice. Twenty-eight male c57bl/6 mice (6 months old) received ayahuasca or water (1.5 mL/kg, orally) twice a week for 12 months and were tested in the Morris water maze (MWM), open field and elevated plus maze (EPM) tasks before and after treatment. During aging, there was significant impairment in the evocation (but not acquisition) of spatial reference memory and in habituation to the open field. There was also a decrease in locomotor activity in the open field and EPM tests, whereas the anxiety parameters were unaltered. Ayahuasca treatment did not alter any of these parameters associated with aging. These findings indicate that chronic exposure to ayahuasca during aging did not affect memory in mice.

An ontogenic study of the behavioral effects of chronic intermittent exposure to ayahuasca in mice

Ayahuasca is a beverage obtained from decoctions of the Banisteriopsis caapi plus Psychotria viridis. In religious contexts, ayahuasca is used by different age groups. However, little is known of the effects of ayahuasca during ontogenic development, particularly with regard to the functional characteristics of the central nervous system. Animal models are useful for studying the ontogenic effects of ayahuasca because they allow exclusion of the behavioral influence associated with the ritualistic use. We investigated the effects of exposure to ayahuasca (1.5 mL/kg, orally, twice a week) on memory and anxiety in C57BL/6 mice, with the post-natal day (PND) being used as the ontogenic criterion for classification: childhood (PND21 to PND35), adolescence (PND35 to PND63), adulthood (PND90-PND118), childhood-adolescence (PND21 to PND63), childhood-adulthood (PND21 to PND118) and adolescence-adulthood (PND35 to PND118). One day after the last ayahuasca exposure, the mice were subjected to the Morris water maze (MWM), open field and elevated plus maze tasks (EPM). Ayahuasca did not affect locomotion in the open field or open arms exploration in the EPM, but increased the risk assessment behavior in the childhood group. Ayahuasca did not cause any change in acquisition of spatial reference memory in the MWM task, but decreased the time spent on the platform quadrant during the test session in the adolescence group. These results suggest that, in mice, exposure to ayahuasca in childhood and adolescence promoted anxiety and memory impairment, respectively. However, these behavioral changes were not long-lasting since they were not observed in the childhood-adulthood and adolescence-adulthood groups.

Effects of ganglioside G(M1) and erythropoietin on spinal cord lesions in rats: functional and histological evaluations

OBJECTIVE: To evaluate the functional and histological effects of ganglioside G(M1) and erythropoietin after experimental spinal cord contusion injury. METHODS: Fifty male Wistar rats underwent experimental spinal cord lesioning using an NYU-Impactor device and were randomly divided into the following groups, which received treatment intraperitoneally. The G(M1) group received ganglioside G(M1) (30 mg/kg); the erythropoietin group received erythropoietin (1000 IU/kg); the combined group received both drugs; and the saline group received saline (0.9%) as a control. A fifth group was the laminectomy group, in which the animals were subjected to laminectomy alone, without spinal lesioning or treatment. The animals were evaluated according to the Basso, Beattie and Bresnahan (BBB) scale, motor evoked potential recordings and, after euthanasia, histological analysis of spinal cord tissue. RESULTS: The erythropoietin group had higher BBB scores than the G(M1) group. The combined group had the highest BBB scores, and the saline group had the lowest BBB scores. No significant difference in latency was observed between the three groups that underwent spinal cord lesioning and intervention. However, the combined group showed a significantly higher signal amplitude than the other treatment groups or the saline group (p<0.01). Histological tissue analysis showed no significant difference between the groups. Axonal index was significantly enhanced in the combined group than any other intervention (p<0.01). CONCLUSION: G(M1) and erythropoietin exert therapeutic effects on axonal regeneration and electrophysiological and motor functions in rats subjected to experimental spinal cord lesioning and administering these two substances in combination potentiates their effects.

Central nervous system stimulant actions of Alpinia galanga (L.) rhizome: A preliminary study.

Methanolic and ethyl acetate extract of A. galanga showed significant central nervous system (CNS) stimulant activity in mice using actophotometer and rotarod test. CNS stimulation at a dose of 500 mg/kg was comparable with standard drugs caffeine and amphetamine derivative modalart. The extracts did not shown any depressant effect in forced swim or tail suspension tests. It can be concluded that A. galanga rhizome may have stimulant activity in mice and the active constituents responsible for this effect is present both in crude methanolic extract as well as in ethyl acetate fraction of methanolic extract of this plant species.

Association of acepromazine with propofol in giant amazon turtles Podocnemis expansa reared in captivity / Associação da acepromazina com propofol em tartarugas-da-amazônia Podocnemis expansa criadas em cativeiro

PURPOSE: To evaluate the effects of different concentrations of an anesthetic association in giant amazon turtles (Podocnemis expansa). METHODS: Twenty healthy P. expansa of both sexes weighing between 1.0 and 1.5kg commercially bred in the Araguaia River Valley, Goias, Brazil, were separated into two groups (G1 n=10 and G2 n=10). Each group received a respective protocol: P1= acepromazine (0.5 mg/kg IM) and propofol (5 mg/kg IV) and P2 = acepromazine (0.5 mg/kg IM) and propofol (10 mg/kg IV). The acepromazine was administered in the left thoracic member and the propofol in the cervical vertebral sinus. Assessments were made of the anesthetic parameters of locomotion, muscle relaxation, response to pain stimuli in the right thoracic and pelvic members and heartbeat. RESULTS: The anesthetic induction time was the same for both protocols (P1 and P2); however the P2 effects were of a longer duration. CONCLUSION: The sedation achieved with both protocols (P1 and P2) were satisfactory for the biological sample collection, physical examinations and minor surgeries on this species.

OBJETIVO: Avaliar os efeitos de uma associação anestésica com diferentes concentrações em tartarugas-da-amazônia (Podocnemis expansa). MÉTODOS: Vinte P. expansa, hígidas, de ambos os sexos, com massa corporal entre 1,0 e 1,5 kg, de um criatório comercial localizado no vale do rio Araguaia, Goiás, Brasil, foram distribuídas em dois grupos (G1 n=10 e G2 n=10). Cada grupo recebeu um protocolo sendo: P1 = acepromazina (0,5 mg/kg IM) e propofol (5 mg/kg IV) e P2 = acepromazina (0,5 mg/kg IM) e propofol (10 mg/kg IV), aplicados nos grupos G1 e G2, respectivamente. A acepromazina foi aplicada no membro torácico esquerdo e o propofol no seio vertebral cervical. Foram avaliados os parâmetros anestésicos: locomoção, relaxamento muscular, resposta aos estímulos dolorosos no membro torácico direito e nos membros pelvinos e frequência cardíaca. RESULTADOS: O tempo de indução anestésica foi o mesmo para ambos os protocolos (P1 e P2), porém o P2 apresentou efeitos mais duradouros. CONCLUSÃO: As sedações obtidas por esses protocolos (P1 e P2) foram satisfatórias para a colheita de amostras biológicas, exames físicos e realização de pequenos procedimentos cirúrgicos nesta espécie.

Association of midazolam with ketamine in giant Amazon river turtles Podocnemis expansa breed in captivity / Associação de midazolam com cetamina em tartarugas da Amazônia Podocnemis expansa de cativeiro

PURPOSE: Evaluate the effects of two anesthetic associations in giant Amazon river turtles (P. expansa). METHODS: Twenty P. expansa, healthy, of both sexes, with weights between 1.0 and 1.5 kg of a commercial breeding facility located in the valley of the Araguaia River, Goiás, Brazil, were divided into two groups ( G1 n = 10 and G2 n = 10). Each group received a protocol being: P1 = midazolam (2 mg/kg IM) and ketamine (20 mg/kg IM) and P2 = midazolam (2 mg/kg IM) and ketamine (60 mg/kg IM), applied on G1 and G2, respectively. The drugs were applied in the left forelimb. The clinical parameters evaluated were: locomotion, muscle relaxation, response to pain stimuli in the right thoracic and pelvic members and heart rate. These assessments were made at time 0 (immediately after injection) and times of 5, 10, 20, 30, 45, 60, 90, 120, 150 and 180 minutes after the injections. RESULTS: Group 2 showed a higher heart rate than G1 and more rapid and prolonged immobilization. CONCLUSION: The sedation scores obtained by these protocols (P1 and P2) were satisfactory, with possible pharmacological contention for collecting biological samples and physical examination in P. expansa.

OBJETIVO: Avaliar os efeitos de duas associações anestésicas em tartarugas da Amazônia em (Podocnemis expansa). MÉTODOS: Vinte P. expansa, hígidas, de ambos os sexos, com massa corporal entre 1,0 e 1,5 kg, de um criatório comercial localizado no vale do rio Araguaia, Goiás, Brasil, foram distribuídas em dois grupos (G1 n=10 e G2 n=10). Cada grupo recebeu um protocolo sendo: P1 = midazolam (2 mg/kg IM) com cetamina (20 mg/kg IM) e P2 = midazolam (2 mg/kg IM) com cetamina (60 mg/kg IM), aplicados nos grupos G1 e G2, respectivamente. Os fármacos foram aplicados no membro torácico esquerdo. Os parâmetros clínicos avaliados foram: locomoção, relaxamento muscular, resposta aos estímulos dolorosos nos membros torácico direito e pelvinos e freqüência cardíaca. Essas avaliações foram feitas no tempo 0 (imediatamente após a injeção) e nos tempos 5, 10, 20, 30, 45, 60, 90, 120, 150 e 180 minutos após as injeções. RESULTADOS: O G2 apresentou maior freqüência cardíaca que o G1 e imobilização mais rápida e prolongada. CONCLUSÃO: As sedações obtidas por esses protocolos (P1 e P2) foram satisfatórias, sendo possível a contenção farmacológica para a coleta de amostras biológicas e exame físico em P. expansa.

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although cross-sensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9 percent NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

Effects of valproic acid, a histone deacetylase inhibitor, on improvement of locomotor function in rat spinal cord injury based on epigenetic science

The primary phase of traumatic spinal cord injury [SCI] starts by a complex local inflammatory reaction such as secretion of pro-inflammatory cytokines from microglia and injured cells that substantially contribute to exacerbating pathogenic events in secondary phase. Valproic acid [VPA] is a histone deacetylase inhibitor. Acetylation of histones is critical to cellular inflammatory and repair processes. In this study, rats were randomly assigned to five experimental groups [laminectomy, untreated, and three VPA-treated groups]. For SCI, severe contusion was used. In treated groups, VPA was administered intraperitoneally at doses of 100, 200 and 400 mg/kg daily three hours after injury for 7 days. To compare locomotor improvement among experimental groups, behavioral assessments were performed by the Basso, Beattie and Bresnahan [BBB] rating scale. The expression of neurotrophins was evaluated by RT-PCR and real-time PCR. VPA administration increased regional brain-derived neurotrophic factor and glial cell-derived neurotrophic factor mRNA levels. Local inflammation and the expression of the lysosomal marker ED1 by activated macrophages/microglial cells were reduced by VPA and immunoreactivity of acetylated histone and microtubule-associated protein were increased. The results showed a reduction in the development of secondary damage in rat spinal cord trauma with an improvement in the open field test [BBB scale] with rapid recovery

Pharmacological restraint of captivity giant Amazonian turtle Podocnemis expansa (Testudines, Podocnemididae) with xylazine and propofol / Contenção farmacológica de tartaruga da Amazônia Podocnemis expansa (Testudines, Podocnemididae) de cativeiro com xilazina e propofol

PURPOSE: Identify a technique to induce brief sedation and hypnosis in Podocnemis expansa. METHODS: Twenty commercially bred P. expansa, weighing on average 1.2 ± 0.24 kg, were subjected to two protocols: G1 was given 1.5 mg/kg IM of xylazine and 5 mg/kg IV of propofol, while G2 received 1.5 mg/kg IM of xylazine and 10 mg/kg IV of propofol. The drugs were applied, respectively, in the left thoracic member and in the cervical vertebral sinus. Assessments were made of the anesthetic parameters of locomotion, muscle relaxation, response to pain stimuli in the right thoracic members, pelvic members and tail, easy handling and heartbeat, as well as ambient temperature and glycemic level. RESULTS: A consistent hypnotic effect was recorded 49.6 ± 22.1 seconds in G2 and after 58.2 ± 55.1 in G1. All the animals of G2 recovered in 198 minutes, and those of G1 in 156 minutes. CONCLUSION: The hypnosis achieved with these associations was satisfactory, and G1 was as efficient as G2, allowing for the pharmacological restraint for the collection of biological samples, physical examinations and minor surgeries on these species.

OBJETIVO: Identificar uma técnica para se induzir sedação e hipnose em Podocnemis expansa. MÉTODOS: Vinte Podocnemis expansa de criatório comercial, com média de peso 1,2 ± 0,24 kg, foram submetidas a dois protocolos: G1 recebeu xilazina 1,5 mg/kg IM e propofol 5 mg/kg IV e o G2 xilazina 1,5 mg/kg IM e propofol 10 mg/kg IV. As drogas foram aplicadas no membro torácico esquerdo e no seio vertebral cervical, respectivamente. Observaram-se os parâmetros anestésicos: locomoção, relaxamento muscular, resposta aos estímulos dolorosos no membro torácico direito, nos membros pelvinos e na cauda, facilidade de manipulação e freqüência cardíaca, além da temperatura ambiental e glicemia. RESULTADOS: Um efeito hipnótico consistente foi observado aos 49,6 ± 22,1 segundos no G2 e 58,2 ± 55,1 segundos no G1. A recuperação de todos os animais do G2 ocorreu em 198 minutos, e em 156 minutos no G1. CONCLUSÃO: A hipnose obtida por essas associações foi satisfatória e o Grupo 1 foi tão eficiente quanto o Grupo 2, o que possibilita a contenção farmacológica para coleta de amostras biológicas, exames físicos e realização de pequenas cirurgias nesta espécie.

Effects of azadirachtin on mortality, fertilization, and swimming speed in larvae of the cane toad, Bufo marinus (Anura: Bufonidae).

Experiments were conducted to assess the effects of azadirachtin (AZ) on survival capacity, fertilization success, and swimming speed in larval stages of the cane toad, Bufo marinus . LC50 values (96-hr) for various larval stages exposed to 0.50 mg/l AZ were as follows: 5.35 (stage 12), 5.77 (stage 16), 787 (stage 20), 13.43 (stage 24), and 21.54 (stage 30). Tadpoles did not exhibit any apparent disorientation or production of mucous in response to AZ concentrations ranging from 0.3 to 0.5 mg/l. Mortality was significantly higher at 0.50 mg/l AZ than at lower concentrations. At 0.50 mg/l, mortality rate decreased significantly from 36% for stage 12 tadpoles, to 24% for stage 20 tadpoles. Mortality for early stages (stage 12) dropped significantly, from 36% at 0.50 mg/l, to 21% at 0.40 mg/l AZ There were no significant differences in percent mortality for any developmental stage at an AZ concentration of 0.3 mg/l, or for controls (no AZ). Exposure of gametes to 0.30 mg/l AZ did not reduce fertilization success as compared to controls (89.8 vs. 83.7%). At 0.40 mg/l, percent fertilization decreased significantly (68.8%). This effect was even more pronounced at 0.50 mg/l. No significant difference was found in swimming speeds between controls and subjects exposed to 0.30 mg/l AZ. However, at a concentration of 0.40 mg/l, tadpoles required a significantly longer period of time to swim a distance of 140 cm as compared to controls. The potential impact of AZ on amphibian populations is discussed.