RESUMO
TsTX is an á-type sodium channel toxin that stimulates the discharge of neurotransmitters from neurons. In the present study we investigated which neurotransmitters are released in the hippocampus after TsTX injection and if they are responsible for electrographic or histopathological effects. Microdialysis revealed that the toxin increased glutamate extracellular levels in the hippocampus; however, levels of gamma-aminobutyric acid (GABA), glycine, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were not significantly altered. Neurodegeneration in pyramidal cells of hippocampus and electroencephalographic alterations caused by the toxin were blocked by pretreatment with riluzole, a glutamate release inhibitor. The present results suggest a specific activity of TsTX in the hippocampus which affects only glutamate release.
Assuntos
Humanos , Animais , Ratos , Hipocampo , Neurotransmissores , Venenos de Escorpião/toxicidadeRESUMO
Tityus serrulatus is the most venomous scorpion in Brazil; however, it is not known whether its venom causes any harm to the offspring whose mothers have received it. This study investigates whether the venom of T. serrulatus may lead to deleterious effects in the offspring, when once administered to pregnant rats at a dose that causes moderate envenomation (3mg/kg). The venom effects were studied on the 5th and on the 10th gestation day (GD5 and GD10). The maternal reproductive parameters of the group that received the venom on GD5 showed no alteration. The group that received the venom on GD10 presented an increase in post-implantation losses. In this group, an increase in the liver weight was also observed and one-third of the fetuses presented incomplete ossification of skull bones. None of the groups that received the venom had any visceral malformation or delay in the fetal development of their offspring. The histopathological analysis revealed not only placentas and lungs but also hearts, livers and kidneys in perfect state. Even having caused little effect on the dams, the venom may act in a more incisive way on the offspring, whether by stress generation or by a direct action.
Assuntos
Animais , Feminino , Ratos , Feto/anormalidades , Prenhez , Venenos de Escorpião/toxicidade , Ratos WistarRESUMO
Haloperidol is a receptor D2 antagonist frequently used in the treatment of schizophrenic patients. Haloperidol increased prolactin release from anterior pituitary gland, and prolactin modulates immune system activity. Groups of six male and female rats received an acute 2 mg/kg haloperidol treatment (E1), or a long-term (E2) haloperidol treatments (2 mg/kg/day for 21 days); control rats were treated similarly, but with control solution (groups C1 and C2, respectively). In this work long-term haloperidol treatment (E2) increased macrophage spreading, phagocytosis and NO release in male and female rats. However, acute haloperidol treatment (E1) did not change macrophage activity. Corticosterone and prolactin serum levels were increased after acute (E1) and long-term (E2) haloperidol treatments in male and female rats, being this increment higher in female. Macrophage of male and female rats presented the same pattern of alterations after acute and long-term haloperidol treatments. Haloperidol-induced macrophage activation was discussed in the light of a possible indirect effect through prolactin increments in rats, or, alternatively, as a consequence of a direct action of macrophage dopamine receptor.
Assuntos
Antipsicóticos/farmacologia , Corticosterona/sangue , Haloperidol/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Prolactina/sangue , Animais , Feminino , Peróxido de Hidrogênio/metabolismo , Macrófagos Peritoneais/metabolismo , Masculino , Óxido Nítrico/metabolismo , Fagocitose/efeitos dos fármacos , Ratos , Ratos Wistar , Explosão Respiratória/efeitos dos fármacos , Caracteres Sexuais , Estimulação Química , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Haloperidol is a receptor D2 antagonist frequently used in the treatment of schizophrenic patients. Haloperidol increased prolactin release from anterior pituitary gland, and prolactin modulates immune system activity. Groups of six male and female rats received an acute 2 mg/kg haloperidol treatment (E1), or a long-term (E2) haloperidol treatments (2 mg/kg/day for 21 days); control rats were treated similarly, but with control solution (groups C1 and C2, respectively). In this work long-term haloperidol treatment (E2) increased macrophage spreading, phagocytosis and NO release in male and female rats. However, acute haloperidol treatment (E1) did not change macrophage activity. Corticosterone and prolactin serum levels were increased after acute (E1) and long-term (E2) haloperidol treatments in male and female rats, being this increment higher in female. Macrophage of male and female rats presented the same pattern of alterations after acute and long-term haloperidol treatments. Haloperidol-induced macrophage activation was discussed in the light of a possible indirect effect through prolactin increments in rats, or, alternatively, as a consequence of a direct action of macrophage dopamine receptor.
Assuntos
Animais , Ratos , Haloperidol , Macrófagos , Corticosterona , ProlactinaRESUMO
Scorpion venom neurotoxins are responsible for toxicity and pharmacological effects. They are active in sodium and potassium channels leading to an increase in the release of neurotransmitters, such as glutamate. Glutamate is found in large quantities in the hippocampus (HPC) and is involved in the long-term potentiation (LTP) induction. The HPC is known to be related to certain kinds of memory. The aim of this study is to evaluate the effects of Tityus serrulatus TS-8F toxin on rat behavior with emphasis on learning and memory. We analyzed the effects of different doses of TS-8F on rat behavior in home cages, open-field (habituation), inhibitory avoidance, T-maze, and hippocampus morphology. In the first two experiments, 0.05µg/animal dose of TS-8F did not cause convulsion but led to a decrease in locomotion (LO) frequency in the open-field first session. During the second session, rats receiving 0.03µg/animal TS-8F showed a decrease in LO and rearing frequency (RE); controls only showed decreased LO; and those receiving 0.05µg/animal showed no significant changes. In inhibitory avoidance, T-maze, and HPC morphology experiments no significant differences were observed. It is concluded that TS-8F may exert some influence in rat learning and memory and seems to be useful as a pharmacological tool. Further research is required to elucidate all possible uses of this toxin.
Assuntos
Ratos , Animais , Masculino , Toxinas Biológicas , Aprendizagem , Memória , Neurotoxinas , Venenos de Escorpião/efeitos adversos , Venenos de Escorpião/toxicidade , Ratos Wistar , Convulsões/induzido quimicamenteRESUMO
Scorpion venoms contain low molecular weight basic polypeptides, neurotoxins, that are the principal toxic agents. These toxins act on ion channels, promoting a derangement that may result in an abnormal release of neurotransmitters. In the present study we investigated some of the effects of the F, H and J fractions isolated from Tityus serrulatus scorpion venom on the central nervous system of rodents. The venom was partially purified by gel filtration chromatography. The neurotoxic effect of these fractions was studied on convulsive activity after intravenous injection, and on electrographic activity and neuronal integrity of rat hippocampus when injected directly into this brain area. The results showed that intravenous injection of the F and H fractions induced convulsions, and intrahippocampal injection caused electrographic seizures in rats and neuronal damage in specific hippocampal areas. Fraction J injected intravenously reduced the general activity of mice in the open field but induced no changes when injected into the brain. These results suggest that scorpion toxins are able to act directly on the central nervous system promoting behavioural, electrographic and histological modifications.
Assuntos
Neurotoxinas/toxicidade , Venenos de Escorpião/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Fracionamento Químico , Cromatografia em Gel , Eletroencefalografia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/fisiopatologia , Injeções Intravenosas , Masculino , Camundongos , Neurotoxinas/química , Neurotoxinas/isolamento & purificação , Ratos , Ratos Wistar , Venenos de Escorpião/química , Venenos de Escorpião/isolamento & purificação , Convulsões/induzido quimicamenteRESUMO
It has been previously shown that the crude venom of Tityus serrulatus can cause convulsions. This study was designed to investigate the neurotoxic effects of B, C, G, and K fractions isolated from this venom. Intravenous injection of these fractions in mice (0.6 - 6.0 mg/kg body weight) showed that the C fraction is a potent convulsant and G fraction decreased the threshold for tonic hand limb extension elicited by transauricular electroshock. Unilateral injection of B, C, and K fractions, but not G fraction, into the spikes and epileptic discharges that began in the hippocampus and evolved to the cortex. The following motor signs were observed: movements of facial muscles, wet dog shake, immobility, myoclonus, wild-running with clonus, and in some cases, loss of postural control. Intrahippocampal injection of B, C, and K fraction, but not G fraction, caused neuronal loss at the injection site as well as in other hippocampal areas. The effect of these fractions on epileptiform activity and on neuronal loss was dose-dependent. The severity of the epileptiform activity in the ipsilateral hippocampus correlated with the severity of the neuronal loss. The electrographic, behavioral, and histological changes induced by b, C, and K fractions were similar to those obtained with other drugs that are commonly used to induce convulsion. The convulsant effects of the crude venom may be caused by the fractions studied in this work.
Assuntos
Masculino , Ratos , Camundongos , Comportamento Animal/efeitos dos fármacos , Eletroencefalografia , Hipocampo/efeitos dos fármacos , Convulsões/induzido quimicamente , Venenos de Escorpião/toxicidade , Convulsões/induzido quimicamente , Estudos de Casos e Controles , Ratos Wistar , Análise de Variância , Relação Dose-Resposta a Droga , Venenos de Escorpião/isolamento & purificaçãoRESUMO
The effects of intrahippocampal administration of a neuropeptide (TS-8F toxin) isolated from Tityus serrulatus scorpion venom have been determined on behavior, limbic seizures, and neuronal degeneration in rats. Behavioral observation showed orofacial automatism, wet dog shakes, and myoclonus. Concomitantly, the electroencephalographic record showed high-frequency and high-voltage spikes that evolved to seizure activity in the hippocampus and cortex. Seven days after TS-8F toxin microinjection, neuronal damage was observed in CA1 and CA2 pyramidal cells and in granular cells of the dentate gyrus. The results suggest that TS-8F toxin may be responsible, at least in part, by the epileptic effects observed with the crude venom. Thus, this toxin may be a useful tool in the study of some neurobiological process.
Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Neuropeptídeos/toxicidade , Neurotoxinas/toxicidade , Venenos de Escorpião/toxicidade , Sequência de Aminoácidos , Animais , Comportamento Animal/fisiologia , Encéfalo/fisiopatologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Eletroencefalografia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Dados de Sequência Molecular , Degeneração Neural/induzido quimicamente , Degeneração Neural/patologia , Neuropeptídeos/química , Neuropeptídeos/isolamento & purificação , Neurotoxinas/química , Neurotoxinas/isolamento & purificação , Ratos , Ratos Wistar , Venenos de Escorpião/química , Convulsões/induzido quimicamenteRESUMO
This study was designed to investigate the effect of T. serrulatus scorpion venom on dopamine (DA) and gamma amino butyric acid (GABA) concentrations in different regions of the brain. The ratio of homovanillic acid (HVA) to DA, and the glutamic acid decarboxylase (GAD) activity were determined following intravenous or intracerebral venom injections. The increase in the HVA/DA ratio in the striatum after i.v. or intrastriatal injection could indicate an increase in DA turnover. One hour after i.v. injection of the venom GAD activity was shown to be decreased in the striatum and hypothalamus. After 24 hr GAD activity increased in the striatum and decreased in the hypothalamus and brain stem. These results could indicate different effects of the venom on the GABA system in different areas of the brain. After intrastriatal injection of the scorpion venom, the animals showed stereotyped behavior and rotation activity. Following intrahippocampal injection, myoclonus and orofacial automatisms, which constitute pro-convulsive signals, were observed. These behavioral alterations could be, at least in part, related to the GABA and dopamine alterations caused by the venom, since stereotypy, circling behavior and convulsions are dependent on dopamine and/or GABA.
Assuntos
Encéfalo/efeitos dos fármacos , Dopamina/metabolismo , Neurotoxinas/toxicidade , Venenos de Escorpião/toxicidade , Ácido gama-Aminobutírico/metabolismo , Análise de Variância , Animais , Encéfalo/metabolismo , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Glutamato Descarboxilase , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ácido Homovanílico/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Injeções Intraventriculares , Masculino , Microinjeções , Atividade Motora/efeitos dos fármacos , Neurotoxinas/administração & dosagem , Neurotoxinas/metabolismo , Ratos , Ratos Wistar , Venenos de Escorpião/administração & dosagem , Venenos de Escorpião/metabolismo , Convulsões/induzido quimicamente , Comportamento Estereotipado/efeitos dos fármacosRESUMO
Changes induced by aging in dopaminergic activity of male and female rats were compared by behavioral and neurochemical methods. Young (3 months) and old (23 months) rats were used. Aging decreased animal activity in the open field and increased apomorphine-induced stereotyped behavior. No differences in open field data were observed between males and females. Young and aged female rats had higher striatal DA and HVA levels than males; aging induced a decrease in both striatal DA and HVA levels in males, but not in females. No changes in HVA/DA ratios were observed among the different groups. These results show that aging reduces nigrostriatal activity as well as nigrostriatal DA levels. Furthermore, they indicate that time course events related to aging differ between males and females.
Assuntos
Envelhecimento/fisiologia , Comportamento Animal/fisiologia , Dopamina/fisiologia , Receptores Dopaminérgicos/fisiologia , Animais , Apomorfina/farmacologia , Comportamento Animal/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiologia , Feminino , Ácido Homovanílico/metabolismo , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Ratos , Ratos Wistar , Receptores Dopaminérgicos/efeitos dos fármacos , Fatores Sexuais , Comportamento Estereotipado/efeitos dos fármacos , Comportamento Estereotipado/fisiologiaRESUMO
Changes induced by aging in dopaminergic activity of male and female rats were compared by behavioral and neurochemical methods. Young (3 months) and old (23 months) rats were used. Aging decreased animal activity in the open field and increased aponiorphine-induced stereotyped behavior. No differences in open field data were observed between males and females. Young and aged female rats had higher striatal DA and HVA levels than males; aging induced a decrease in both striatal DA and HVA levels in males, but not in females. No changes in HVA/DA ratios were observed among the different groups. These results show that aging reduces nigrostriatal activity as well as nigrostriatal DA levels. Furthermore, they indicate that time course events related to aging differ between males and females
Assuntos
Animais , Comportamento Sexual Animal/classificação , Envelhecimento , DopaminaRESUMO
This study was designed to investigate the effect of T. serrulatus scorpion venom on dopamine (DA) and gamma amino butyric acid (GABA) concentrations in different regions of the brain. The ratio of homovanillic acid (HVA) to DA, and the glutamic acid decarboxylase (GAD) activity were determined following intravenous or intracerebral venom injections. The increase in the HYA/DA ratio in the striatum after i.v. or intrastriatal injection could indicate an increase in DA turnover. One hour after i.v. injection of the venom GAD activity was shown to be decreased in the striatum and hypothalamus. After 24 hr GAD activity increased in the striatum and decreased in the hypothalamus and brain stem. These results could indicate different effects of the venom on the GABA system in different areas of the brain. After intrastriatal injection of the scorpion venom, the animals showed stereotyped behavior and rotation activity. Following intrahippocampal injection, myoclonus and orofacial automatisms, which constitute pro-convulsive signals, were observed. These behavioral alterations could be, at least in part, related to the GABA and dopamine alterations caused by the venom, since stereotypy, circling behavior and convulsions are dependent on dopamine and/or GABA.
Assuntos
Ratos , Venenos de Escorpião/classificação , Venenos de Escorpião/toxicidade , CérebroRESUMO
This study was designed to investigate the convulsant effects of T. serrulatus scorpion venom in rats. Pretreatment of rats with venom increased the minimum convulsant dose of picrotoxin, impaired convulsion generalization and displaced to the left the dose-response curve for picrotoxin. It also decreased the intensity but prolonged the duration of seizures caused by pentylenetetrazol injection. Microinjection of the venom into the dorsal hippocampus induced behavioural alterations and epileptiform waves in the EEG. Venom also altered the threshold for, and intensity of, convulsions induced in different experimental models of epilepsy. Different fractions of the venom may be responsible for these different effects. Therefore, purification of venom toxins is necessary for the complete understanding of the present results.
Assuntos
Comportamento Animal/efeitos dos fármacos , Convulsivantes/toxicidade , Eletroencefalografia/efeitos dos fármacos , Venenos de Escorpião/toxicidade , Animais , Relação Dose-Resposta a Droga , Eletrodos , Epilepsia/induzido quimicamente , Hipocampo , Masculino , Microinjeções , Pentilenotetrazol , Picrotoxina , Ratos , Ratos WistarRESUMO
This study was designed to investigate the convulsant effects of T. serrulatus scorpion venom in rats. Pretreatment of rats with venom increased the minimum convulsant dose of picrotoxin, impaired convulsion generalization and displaced to the left the dose-response curve for picrotoxin. It also decreased the intensity but prolonged the duration of seizures caused by pentylenetetrazol injection. Microinjection of the venom into the dorsal hippocampus induced behavioural alterations and epileptiform waves int he EEG. Venom also altered the threshold for, and intensity of, convulsions induced in different experimental models of epilepsy. Different fractions of the venom may be responsible for these different effects. Therefore, purification of venom toxins is necessary for the complete understanding of the present results.
Assuntos
Animais , Venenos de Escorpião/classificação , Venenos de Escorpião/toxicidade , EpilepsiaRESUMO
The effect of lithium (2.0 mEq/kg, IP) on dopaminergic supersensitivity induced by long-term estrogen treatment (0.25 mg/day, SC) was investigated. Ovariectomized rats were treated for 28 days with estrogen and/or lithium and 6 days after the last administration all animals were observed for apomorphine-induced stereotyped behavior (1.0 mg/kg, SC). The abrupt withdrawal from long-term estrogen treatment increased rats' sensitivity to apomorphine but lithium administration was able to prevent this increase. Lithium alone produced no effect on stereotyped behavior. It was suggested that lithium may antagonize the estrogen effect on the nigrostriatal dopamine system.
Assuntos
Estrogênios/farmacologia , Lítio/farmacologia , Receptores Dopaminérgicos/efeitos dos fármacos , Animais , Apomorfina/farmacologia , Feminino , Ovariectomia , Ratos , Ratos Endogâmicos , Comportamento Estereotipado/efeitos dos fármacosRESUMO
1. The effects of ovariectomy and/or of female hormonal treatments on open-field behavior, apomorphine-induced stereotypies and haloperidol-induced catalepsy were studied in rats. 2. Rat's locomotion frequency was significantly decreased by 17 beta-estradiol and estradiol plus progesterone treatments; this open-field parameter was not affected by progesterone administration per se. 3. 17 beta-estradiol and progesterone treatments, alone or in combination decreased apomorphine-stereotyped behavior. 4. Haloperidol effects were higher in both 17 beta-estradiol and 17 beta-estradiol plus progesterone treated rats. 5. Progesterone treatment alone, decreased the duration of catalepsy induced by the minor (1.0 mg/kg) neuroleptic dose. 6. These results were discussed in the light of a possible interference of estrogen and/or progesterone on dopaminergic transmission at the level of the nigroestratial pathway.
Assuntos
Comportamento Animal/efeitos dos fármacos , Dopamina/fisiologia , Estrogênios/farmacologia , Progesterona/farmacologia , Animais , Álcoois Benzílicos/farmacologia , Catalepsia/induzido quimicamente , Catalepsia/fisiopatologia , Feminino , Haloperidol/farmacologia , Atividade Motora/efeitos dos fármacos , Ovariectomia , Ratos , Ratos Endogâmicos , Comportamento Estereotipado/efeitos dos fármacosRESUMO
1. The effects of ovariectomy and of estrogen administration were determined on some dopamine-related behaviors. 2. Haloperidol withdrawal induced a progressive increase in locomotion and rearing frequencies of female rats observed in an open-field. This increase started earlier and was greater in ovariectomized than in sham-operated animals. 3. Repeated administration of increasing doses of 17-beta-estradiol (from 0.05 to 0.3 mg/kg once daily, for 28 days) significantly decreased apomorphine-induced stereotyped behavior in ovariectomized rats, 30 min after the last hormone injection. 4. Withdrawal from long-term 17-beta-estradiol administration increased the sensitivity of the animals to apomorphine. 5. These results suggest not only an antidopaminergic effect for estrogen but also a possible summation of estrogen and haloperidol withdrawal effects.