RESUMO
Noradrenergic neural systems have been expressly implicated in pathophysiological conditions induced by stress. The majority of experimental evidence supports a central role for brain noradrenaline in mediating the effects of stress and predisposing an organism to stress pathology as well as in producing a well-documented consequence of stress exposure-behavioral depression. This review briefly discusses the noradrenergic (NA) pathways involved, the functioning of NA synapses and their associated receptors and focuses directly upon the effects of stress on NA activity in the brain. These broad categories are discussed in terms of: 1. behavioral versus neurochemical explanations for the effects of stress; 2. the methods used to produce stress; 3. measurement of NA and its major metabolite ("turnover"); 4. regional brain effects of stress; 5. effects of pre-stress alterations in brain NA activity upon subsequent stress-induced brain NA changes; 6. correlation of stress-induced brain NA changes with peripheral manifestations of stress; and 7. predisposing factors in stress-induced neurochemical alterations.
Assuntos
Encéfalo/fisiopatologia , Norepinefrina/fisiologia , Estresse Fisiológico/fisiopatologia , Animais , Antidepressivos/farmacologia , Transtorno Depressivo/etiologia , Suscetibilidade a Doenças , Emoções/fisiologia , Desamparo Aprendido , Humanos , Hipotálamo/metabolismo , Locus Cerúleo/metabolismo , Vias Neurais/fisiopatologia , Neurotransmissores/metabolismo , Ratos , Restrição Física , Serotonina/metabolismo , Estresse Psicológico/fisiopatologia , Transmissão SinápticaRESUMO
The use of restraint or immobilization for investigations of animal physiology, pathology and pharmacology has an extensive history. The major use of this technique has been as a "stressor" for the induction of stress response syndromes in animals. Many such syndromes have been characterized from the behavioral level to the neurochemical concomitants of stress. As a consequence of this particular use of the restraint procedure, much information concerning drug effects on stress response syndromes has been obtained. Indeed, many researchers in the area of gastrointestinal drugs routinely screen their new compounds in a restraint model of gastric stress ulcer. The purpose of this review is to present for researchers, a summary of the methods for, the parameters of, and known drug effects on, restraint-induced pathology. In our experience, this technique has proven to be a very useful one for the examination of both central and peripheral mechanisms of stress-related disorders, as well as for studying drug effects upon these disorders.
Assuntos
Restrição Física/efeitos adversos , Estresse Fisiológico/etiologia , Animais , Cricetinae , Haplorrinos , Camundongos , RatosRESUMO
Since the publication of our initial review of restraint stress in 1986, much work has continued with this technique, either as a tool for the investigation of other pharmacological, physiological, or pathologic phenomena or with restraint stress itself serving as the object of the study. As we noted in 1986, the major use of restraint has been for the induction of stress responses in animals and, more specifically, for the investigation of drug effects, particularly as they affect typical stress-related pathology--gastrointestinal, neuroendocrine, and immunological agents have been extensively studied. In compiling this update on restraint stress and its effects, we noted an increasing emphasis on central nervous system mechanisms in peripheral disease, especially gastrointestinal disease. In particular, many CNS-active agents have been tested for their effects on gastric and duodenal lesion formation and gastric secretion, including antidepressants, antipsychotics, anxiolytics, noradrenergic, serotonergic, dopaminergic, and peptidergic compounds. Some of these agents are especially active in the gastrointestinal tract even when administered centrally, further solidifying the concept of a brain-gut axis. The present update includes studies of: methods and procedures, pre-restraint manipulations, post-restraint/healing effects, and drug effects. In addition, a current bibliography of reports that have employed restraint is included.
Assuntos
Restrição Física , Estresse Psicológico/fisiopatologia , Animais , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/genéticaRESUMO
1. Previous reports of the effects of alpha 2-adrenoceptor stimulation on gastric secretion are inconsistent because it was not clear whether the compounds were activating alpha 2-adrenoceptors and/or newly described imidazoline receptors. In the present experiments, the effects of moxonidine, an I1-imidazoline receptor agonist and antihypertensive agent, on gastric secretion and on experimental gastric mucosal injury were examined. 2. Moxonidine (0.01, 0.1 and 1.0 mg kg-1, i.p.) potently inhibited basal (non-stimulated) gastric acid secretion in conscious rats with an ED50 of 0.04 mg kg-1. Two hours following administration of the highest dose of moxonidine (1.0 mg kg-1), gastric acid output was completely suppressed. Moxonidine also significantly increased intragastric pH, at the two highest doses. 3. The alpha 2-adrenoceptor agonist, clonidine (0.01, 0.1 and 1.0 mg kg-1, i.p.) decreased basal acid secretion at the lowest dose (37%) and at the highest dose (46%), while the intermediate dose did not affect gastric acid output. 4. In an ethanol-induced model of gastric mucosal injury, moxonidine decreased the length of lesions at the lowest and highest doses (0.01 and 1.0 mg kg-1) as well as the number of the lesions, at the highest dose (1.0 mg kg-1). 5. In pylorus-ligated rats, moxonidine significantly decreased acid secretion (all doses), total secretory volume (1.0 mg kg-1) as well as pepsin output (1.0 mg kg-1). 6. In comparison to clonidine, moxonidine appears to be a more potent anti-secretory and gastric-protective compound. These data indicate a potential role for imidazoline receptor agonists in the management of gastroduodenal diseases associated with hypertension. The relative contribution of the central and peripheral effects of moxonidine to these gastrointestinal actions remains to be determined.
Assuntos
Anti-Hipertensivos/farmacologia , Clonidina/farmacologia , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Imidazóis/farmacologia , Receptores de Droga/agonistas , Análise de Variância , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Clonidina/administração & dosagem , Clonidina/uso terapêutico , Modelos Animais de Doenças , Etanol/toxicidade , Mucosa Gástrica/lesões , Mucosa Gástrica/metabolismo , Concentração de Íons de Hidrogênio , Imidazóis/administração & dosagem , Imidazóis/metabolismo , Imidazóis/uso terapêutico , Receptores de Imidazolinas , Injeções Intraperitoneais , Masculino , Pepsina A/metabolismo , Piloro/cirurgia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológicoRESUMO
Virtually all peptides are biologically active following central administration as a consequence of both direct and indirect cellular actions. Direct effects are mainly interactions with specific membrane receptors but may include unions with other components of the receptor/effector complex. Significant indirect biological effects of exogenous peptides, including apparent secretagogue effects on endogenous peptides largely overlooked in practice, result from extensive competition with endogenous peptides for degradative enzymes (peptidases). A consequence of this competition is enhancement of tonic or intermittent activity of endogenous peptides. The pharmacological profile of any peptide reflects or includes, therefore, the spectrum of endogenous peptides that is protected from peptidase action. It is likely that certain pharmacologically active peptides, including a large number of di-, tri- and oligo-peptides, elicit responses mainly or exclusively by competing for peptidases. Therefore, reliable estimates of the relative contributions of direct and indirect actions of exogenous peptides may be difficult, if not impossible, to obtain.
Assuntos
Peptídeos/metabolismo , Inibidores de Proteases/farmacologia , Analgesia , Animais , Hormônios/metabolismo , Humanos , Cinética , Naloxona/farmacologia , Peptídeo Hidrolases/metabolismo , Peptídeos/farmacologia , Transmissão SinápticaRESUMO
Dopamine and its agonists, acting through D1/DA1 receptors, have been shown to be effective protective factors against stress ulcerogenesis. Since anxiety has been related to stress ulcer development, we chose to examine dopaminergic activity in rats screened for the extremes of behaviorally manifest anxiety. High anxious rats develop more stress ulcers and more ethanol ulcers, relative to low anxious animals. High anxious rats require greater amounts of dopaminergic agonists for 50% protection against stress ulcer formation. In conditions of exposure to a stressor, high anxious rats lose amygdalar dopamine at a faster rate than do low anxious rats. These results suggest that anxiety is a significant factor in stress ulcer development and that central dopaminergic function is critically involved in mediating this pathogenetic factor.
Assuntos
Ansiedade/fisiopatologia , Dopaminérgicos/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Estresse Psicológico/complicações , Animais , Etanol , Masculino , Ratos , Ratos Wistar , Úlcera Gástrica/etiologia , Úlcera Gástrica/psicologiaRESUMO
The effect of acute cold-restraint stress on binding of [3H]rauwolscine to alpha 2-adrenoceptors was investigated in 10 regions of rat brain. Acute stress: significantly decreased the density but had no significant effect on the affinity of binding sites in the hippocampus; decreased density and increased affinity in the amygdala; and increased density and decreased the affinity in the midbrain. Seven other brain regions showed no significant changes in binding parameters in response to stress. These results, together with previous findings in this laboratory showed that alteration by restraint stress of noradrenaline levels in amygdala and hippocampus, but not other regions, indicate an association between neurotransmitter turnover and receptor function.
Assuntos
Química Encefálica , Receptores Adrenérgicos alfa/análise , Estresse Fisiológico/metabolismo , Doença Aguda , Animais , Temperatura Baixa/efeitos adversos , Masculino , Ensaio Radioligante , Ratos , Ratos Endogâmicos , Restrição Física , Ioimbina/metabolismoRESUMO
[3H]Etorphine binding was characterized in rat brain homogenates depleted of endogenous opioids from animals acutely and chronically treated with morphine or naloxone and either unstressed or subjected to a 3-h restraint period in the cold. There was significant reduction in the number of high-affinity opiate binding sites in brain tissue from stressed as compared to unstressed animals. Despite the fact that the opiate drug regimens used produce marked behavioral and physiological effects, stress-induced opiate receptor depletion was not influenced by the drugs or by withdrawal. The various drug treatments also failed to produce significant changes in opiate receptor site densities or affinities in either stressed or unstressed animals. We propose that persistent activation of opiate receptors by endogenous opioids released during restraint stress leads to receptor 'down-regulation'.
Assuntos
Encéfalo/metabolismo , Etorfina/metabolismo , Morfinanos/metabolismo , Morfina/farmacologia , Naloxona/farmacologia , Estresse Fisiológico/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Temperatura Baixa , Cinética , Masculino , Morfina/administração & dosagem , Naloxona/administração & dosagem , Ensaio Radioligante , Ratos , Ratos Endogâmicos , Receptores Opioides/efeitos dos fármacos , Receptores Opioides/metabolismoRESUMO
Calcium is important in stimulus-secretion coupling in the gut. We therefore examined a dihydropyridine (nitrendipine), a phenylalkylamine (verapamil) and a benzothiazepine (diltiazem) calcium channel blocker as well as a calcium channel 'agonist', CGP 28392, in several models of gastric function. Nitrendipine significantly decreased stress-induced gastric lesions, but was far less efficacious against 100% ethanol-induced lesions. The anti-ulcer effects of nitrendipine were not reversible with indomethacin, sodium meclofenamate or N-ethylmaleimide. Nitrendipine also significantly reduced basal gastric acid output. Verapamil significantly reduced stress lesions in an indomethacin and meclofenamate-reversible manner, but worsened ethanol ulcers. Verapamil also decreased basal acid secretion. Diltiazem decreased stress lesions (indomethacin- and meclofenamate-reversible), worsened ethanol lesions and slightly reduced acid secretion. CGP 28392 exerted a modest stress gastroprotective effect, decreased ethanol lesions and reduced slightly basal acid secretion. A possible clinical role for gastric calcium channel blockade is raised by these results.
Assuntos
Agonistas dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Estômago/efeitos dos fármacos , Animais , Temperatura Baixa , Etanol , Ácido Gástrico/efeitos dos fármacos , Ácido Gástrico/metabolismo , Masculino , Ratos , Ratos Endogâmicos , Restrição Física , Estômago/fisiopatologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/fisiopatologiaRESUMO
Rats restrained in a cold environment for 3 h developed a high incidence of gastric ulcers. Administration of adenosine receptor agonists prior to a restraint period significantly reduced ulcer formation and severity, and lowered plasma corticosterone levels. This protective effect was blocked by 8-phenyltheophylline, a methylxanthine type adenosine receptor antagonist able to permeate the blood-brain barrier. This finding together with the absolute and relative order of potencies with which adenosine receptor agonists produced their effects suggests that CNS adenosine A1 receptors are involved in blocking and methylxanthines in exacerbating stress-induced gastric pathology.
Assuntos
Encéfalo/metabolismo , Receptores de Superfície Celular/metabolismo , Úlcera Gástrica/metabolismo , Estresse Psicológico/metabolismo , Animais , Temperatura Baixa , Corticosterona/sangue , Masculino , Fenilisopropiladenosina/farmacologia , Ratos , Ratos Endogâmicos , Receptores Purinérgicos , Restrição Física , Estereoisomerismo , Úlcera Gástrica/etiologia , Estresse Psicológico/complicaçõesRESUMO
This study examines the influence of the adrenals and of the vagus nerve on the lesion-worsening action of nitrendipine or verapamil on 75% ethanol-induced gastric mucosal damage in rats. Bilateral adrenalectomy antagonized ethanol lesion aggravation by nitrendipine or verapamil; instead, dose-related lesion reduction was seen. Dexamethasone treatment of adrenalectomized rats restored the lesion-enhancing effects of both Ca2+ channel blockers. Bilateral subdiaphragmatic vagotomy failed to abolish the adverse action of nitrendipine or verapamil on ethanol lesions. The findings suggest that the adrenal corticoids modulate the worsening effect of Ca2+ channel antagonists on ethanol-induced gastric damage; when the influence of the adrenal steroids is removed, these compounds become gastroprotective.
Assuntos
Adrenalectomia , Etanol/toxicidade , Nitrendipino/toxicidade , Úlcera Gástrica/induzido quimicamente , Vagotomia , Verapamil/toxicidade , Animais , Dexametasona/farmacologia , Interações Medicamentosas , Mucosa Gástrica/efeitos dos fármacos , Injeções Intraperitoneais , Masculino , Ratos , Ratos EndogâmicosRESUMO
Ca2+ modulates gastric function and dysfunction as well as the release of cysteine proteases and metalloproteinases which have been implicated in the pathogenesis of gastric mucosal lesions. We thus tested the hypothesis that pretreatment with the Ca2+ chelators, ethylene diamine tetraacetic acid (EDTA) and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) might reduce the experimental gastric mucosal damage induced by restraint cold stress or 1.0 ml of 75% ethanol. Other rats were prepared with chronic indwelling gastric cannulas and the effects of EDTA and EGTA on conscious basal gastric acid output were assessed. In addition, rats were pretreated with EGTA or EDTA prior to pylorus ligation and their effects on acid and pepsin output assessed. Both EDTA and EGTA reduced significantly the extent of ethanol-induced gastric mucosal damage as well as the degree of stress-induced gastric lesions. To further characterize the mechanism of Ca2+ chelator protection against ethanol-induced gastric lesions, some rats were vagotomized or adrenalectomized prior to treatment with EGTA or EDTA, followed by ethanol or stress. Both adrenalectomy and vagotomy abolished gastroprotection by EGTA and slightly reduced that induced by EDTA in both models of experimental gastric mucosal injury. Both EDTA and EGTA reduced significantly basal gastric acid output, an effect which persisted for at least 2 h following their administration. Both compounds also decreased significantly acid and pepsin output in pylorus-ligated rats. We conclude that Ca2+ chelators attenuate both acid-dependent and acid-independent gastric lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Ácido Edético/uso terapêutico , Ácido Egtázico/uso terapêutico , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Úlcera Gástrica/prevenção & controle , Estresse Fisiológico/complicações , Adrenalectomia , Animais , Ácido Gástrico/metabolismo , Ligadura , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/etiologia , VagotomiaRESUMO
Previously we have found that lithium chloride (250 mg/kg i.p.) plus haloperidol (4 mg/kg i.p.), or apomorphine (0.25 mg/kg i.p.) plus thyrotropin releasing hormone (TRH, 20 mg/kg i.p.), elicited a jumping behavior which involves dopaminergic and cholinergic inhibition, and noradrenergic activation. Pretreatment with antiserotonergic agents such as methysergide (5 and 10 mg/kg i.p.) and cyproheptadine (5 mg/kg i.p.) enhanced the jumping behavior induced by these drugs. 5-Methoxy-N,N-dimethyltryptamine (5-MDMT, 5 mg/kg i.p.), a serotonergic receptor agonist, inhibited the jumping behavior. Muscimol, a GABA receptor agonist, at 2 mg/kg, potentiated jumping. GABA receptor antagonists such as bicuculline (4 mg/kg i.p.) and picrotoxin (0.2 and 1 mg/kg i.p.) depressed jumping. An antihistamine agent, diphenhydramine (5 mg/kg i.p.), also potentiated the jumping behavior. Furthermore methysergide (10 mg/kg i.p.), but not muscimol (2 mg/kg i.p.) elicited jumping behavior when combined with clonidine (0.5 mg/kg i.p.), TRH (20 mg/kg i.p.), haloperidol (4 mg/kg i.p.) or atropine (5 mg/kg i.p.). These results suggest that in addition to dopaminergic, cholinergic and noradrenergic mechanisms, serotonergic inhibition may be directly contributing to the initiation of jumping behavior, whereas GABAergic activation appears to be a modulating factor in this behavior.
Assuntos
Atividade Motora/efeitos dos fármacos , Receptores de GABA-A/fisiologia , Receptores de Serotonina/fisiologia , Animais , Apomorfina/farmacologia , Relação Dose-Resposta a Droga , Haloperidol/farmacologia , Lítio/farmacologia , Masculino , Metisergida/farmacologia , Camundongos , Camundongos Endogâmicos , Muscimol/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Receptores de Serotonina/efeitos dos fármacos , Hormônio Liberador de Tireotropina/farmacologiaRESUMO
The effect of both acute and chronic morphine and naloxone on restraint-stress gastric ulcer formation and on basal gastric acid secretion were examined in the conscious rat. Acute morphine administration produced a dose-related decrease in stress ulceration and basal gastric acid secretion. Acute naloxone treatment resulted in a dose-related increase in stress ulcer formation and markedly augmented gastric acid secretion. Naloxone (4.0 mg/kg) antagonized the ulcer-reducing effects at all doses of morphine tested (4.0-32.0 mg/kg). Morphine-dependent rats, restrained during spontaneous or naloxone-precipitated withdrawal, exhibited the most severe ulceration. However, only those subjected to naloxone-precipitated withdrawal produced a significant increase in gastric acid output. Chronic treatment with naloxone or with chronic naloxone followed by morphine (16.0 mg/kg) resulted in augmented stress ulcer formation relative to all acutely treated groups. Both chronic naloxone-treated groups exhibited markedly enhanced gastric secretion. These data suggest that central and/or peripheral opiate receptors can modulate both basal and stress-perturbed gastric function.
Assuntos
Ácido Gástrico/metabolismo , Morfina/farmacologia , Naloxona/farmacologia , Úlcera Gástrica/prevenção & controle , Estresse Psicológico/complicações , Animais , Masculino , Ratos , Ratos Endogâmicos , Restrição Física , Úlcera Gástrica/etiologia , Fatores de TempoRESUMO
Both intraperitoneal and intracerebroventricular (i.c.v.) administration of the monoamine oxidase-B inhibitor L-deprenyl markedly attenuated restraint stress-induced gastric ulcers in rats. L-Deprenyl given i.c.v. attenuated stress ulcers in microgram doses and virtually abolished ulcer formation at a dose of 2.0 micrograms. These data suggest that intact or augmented central dopaminergic function may be an essential component of gastric mucosal protection.
Assuntos
Antiulcerosos , Fenetilaminas/uso terapêutico , Selegilina/uso terapêutico , Úlcera Gástrica/prevenção & controle , Estresse Fisiológico/complicações , Animais , Dopamina/fisiologia , Injeções Intraperitoneais , Injeções Intraventriculares , Masculino , Ratos , Ratos Endogâmicos , Selegilina/administração & dosagem , Estresse Fisiológico/fisiopatologiaRESUMO
1. Rats were prepared with intracerebral cannulas for microinjection of test compounds into various brain regions. 2. Selective dopamine D1 agonists (SKF38393, SKF75670C) and a D1 antagonist (SCH23390) were injected into the cell body regions of the nigrostriatal, mesolimbic and mesocortical dopamine tracts or into a terminal field of these tracts (caudate nucleus, central nucleus of the amygdala and medial prefrontal cortex) prior to gastric ulcer induction by cold-restraint stress or duodenal ulcer induction by cysteamine. 3. The dopamine D1 agonists reduced both stress gastric ulcers and duodenal lesions most significantly when given into either the cell body region or a terminal field of the mesolimbic DA tract with much less effects seen for the nigrostriatal tract. 4. No effects were seen upon infusion of the agonists into the mesocortical cell body or terminal field regions. 5. The D1 antagonist worsened both stress-induced gastric lesions and duodenal lesions if given into mesolimbic regions and, to a much lesser extent when injected into the nigrostriatal tract. 6. No effect of the D1 antagonist was seen upon administration into the mesocortical tract. 7. Central dopamine D1 receptors, particularly in the mesolimbic DA tract, appear to be involved in mediating the gastrointestinal consequences of exposure to stress.
Assuntos
Dopamina/fisiologia , Úlcera Péptica/fisiopatologia , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/farmacologia , Animais , Benzazepinas/farmacologia , Dopaminérgicos/farmacologia , Ligantes , Masculino , Úlcera Péptica/induzido quimicamente , Ratos , Ratos Endogâmicos , Estresse Psicológico/fisiopatologiaRESUMO
1. HCl-extract of poisonous shellfish was injected i.p. into Swiss-Webster mice. 2. Behavioral effects (sluggishness, scratching, huddling, clonic convulsions, respiratory distress and mortality) were noted. 3. Infant mice were more sensitive than were the adults to XTRT toxicity. Estimated LD50 values were; adult: 34.8 ml/kg i.p., infant: 9.6 ml/kg i.p. 4. The mouse model of shellfish-toxicity offers the advantages of a degree of similarity with the human clinical situation and a rapid time course for screening antagonists against shellfish poisoning.
Assuntos
Comportamento Animal/efeitos dos fármacos , Neurotoxinas/toxicidade , Frutos do Mar/toxicidade , Envelhecimento , Animais , Relação Dose-Resposta a Droga , Masculino , Camundongos , Extratos de Tecidos/toxicidadeRESUMO
1. Mice were treated with an extract prepared from poisonous Atlantic mussels. 2. Gastric and duodenal ulcers, duodenal hyperemia and peritoneal ascites resulted from administration of the shellfish extract, with an LD84 of 1.0 ml. 3. Kynurenic acid, an antagonist at excitatory amino acid receptors, protected significantly against gastroduodenal ulcers, ascites and hyperemia when given at 60 or 75 min post-extract. 4. It is likely that the gastrointestinal damage evoked by this extract is due to its domoic acid content and that kynurenic acid may prove useful against domoic acid-induced gastropathy.
Assuntos
Úlcera Duodenal/prevenção & controle , Ácido Cinurênico/uso terapêutico , Intoxicação por Frutos do Mar , Úlcera Gástrica/prevenção & controle , Animais , Sistema Digestório/efeitos dos fármacos , Sistema Digestório/patologia , Úlcera Duodenal/etiologia , Úlcera Duodenal/patologia , Masculino , Camundongos , Úlcera Gástrica/etiologia , Úlcera Gástrica/patologia , Extratos de Tecidos/toxicidadeRESUMO
1. An aqueous acidic extract from poisonous Atlantic coast mussels was injected i.p. into groups of Swiss-Webster mice at the LD84 value (= 40 ml of extract/kg). Body-scratching, clonic convulsions and death were consistently observed in response to XTRT injection. These results are consistent with the presumed presence of the neuroexcitant amino acid, domoic acid, in the contaminated mussels. 2. Kynurenic acid at 300 and 600 mg/kg i.p. protected powerfully and significantly against extract-induced neurotoxicity. Greatest protection was observed when the antidote was administered between 30 and 90 min after injection of the toxic extract.
Assuntos
Bivalves , Ácido Cinurênico/uso terapêutico , Neurotoxinas , Convulsões/induzido quimicamente , Frutos do Mar/toxicidade , Extratos de Tecidos/toxicidade , Animais , Contaminação de Alimentos , Masculino , Camundongos , Convulsões/prevenção & controleRESUMO
A relatively new ulcerogenic procedure, supine restraint-cold, is described. This procedure is simple, effective andproduced a reliably high incidence of gastric glandular lesions in a variety of animal species. In some cases, these lesions penetrate the muscularis mucosa and as such may be called ulcers. They are responsive to known therapeutic agents (cimetidine, aluminum hydroxide). Drugs which modify autonomic activity (scopolamine, carbachol) affect the extent of supine restraint-cold induced gastric lesions. Animals which differ in open-field behaviors indicative of emotionality, show marked differences in gastric lesions induced by this procedure. It is suggested that the supine restraint-cold procedure meets the established criteria for a useful experimental ulcer model [25] and thus represents a viable research tool.