The frog brainstem preparation as a model for studying the central control of breathing in tetrapods

Our frog brainstem preparation revealed mechanisms for the central control of breathing that are in many ways similar to those of mammals. Thus, the basic control mechanisms for air-breathing appear to have been present in the Devonian common ancestors of frogs and mammals and may be common to all lung-breathing vertebrates. Location: The in vitro frog brainstem, including motor nuclei of cranial nerves V to X, maintains frequency and ratio of fictive buccal oscillations to fictive lung inflation episodes comparable with that of the living animal. In this preparation, transaction caudal to V abolishes spontaneous discharge in X but slow, spontaneous discharge in V may remain. Independent central pattern generation is present in the left and right half-brainstems. Chemosensitivity: The frequency of fictive lung inflation increases with decrease in pH within the physiological range. Response to glutamate: Biphasic response, consisting of a pause, followed by a dramatic increase in the frequency of fictive inspirations and positive baseline deflection, followed, in turn, by slow return of the baseline to the control level with frequency remaining above control as long as glutamate is applied. Local application reveals glutamate-sensitive sites in the ventral reticular formation. Response to substance P and physalaemin: Similar to glutamate but the frequency of fictive inspirations decreases below control values. Response to strychnine: The normal temporal sequence in firing of motor neurons of cranial nerves is disrupted and all nerves are synchronously active. The firing sequence of respiratory neurons is consistent with a grouping possibly homologous to the mammalian inspiratory, post-inspiratory and expiratory phases.

Effects of iontophoretically applied naloxone, picrotoxin and strychnine on dorsal horn neuron activities treated with high frequency conditioning stimulation in cats

Transcutaneous electrical nerve stimulation(TENS), acupuncture-needling, and electroacupuncture are useful non-ablative methods in medical practice for relief of pain. These procedures appear to work by causing an increased discharge in afferent nerve fibers which in turn modifies the transmission of impulses in pain pathways. It is known that the mechanism of analagesic effect via these maneuvers are variable depending on the stimulating parameters. For example, the endogenous opioid system is profoundly related to the mechanism when a peripheral nerve stimulation is applied with parameters of low frequency and high intensity. However, when stimulated with parameters of high frequency and high intensity, the reduced activity of dorsal horn neurons is only slightly reversed by a systemic administration of naloxone, a specific opiate antagonist. Thus, the present study was performed to investigate the neurotransmitter that concerns the mechanism of peripheral nerve stimulation with parameters of high frequency and high intensity. We used an iontophoretic application of antagonists of possible related neurotransmitters. The dorsal horn neuron activity which was evoked by squeezing the peripheral cutaneous receptive field, was recorded as an index of pain with a microelectrode at the lumbo-sacral spinal cord. Naloxone, picrotoxin and strychnine were applied at 200nA during a period of conditioning nerve stimulation. We observed the effects of these drugs on the change of dorsal horn neuron activities. The main results of the experiment can be summarized as follows. The spontaneous activity of dorsal horn neurons increased in the presence of glutamate and decreased with GABA. It did not change with naloxone, picrotoxin or strychnine. When naloxone was applied iontophoretically during peripheral nerve stimulation, there was no statistically significant analgesic effect compared with that of the control group. When picrotoxin was applied iontophoretically during peripheral nerve stimulation, the analgesic effect was reduced. When strychnine was applied, the analgesic effect was reduced but did not show a statistically significant difference with the control group. These results suggested that the GABAergic system may have been partially related in the analgesic action of peripheral nerve stimulation with parameters of high frequency and high intensity.

Relacao estrutura-atividade e mecanismo de acao de anticonvulsivantes derivados do 2-sulfamoilbenzoato. 1. Atividade anti-estricnina / Structure-activity relationship and mechanism of anticonvulsant action of 2-sulfamoylbenzoate derivatives. I. Anti-strychinine activity

Com o objetivo de estudar as relacoes quantitativas entre a estrutura quimica e a atividade anti-estricnina em uma serie de derivados 2-sulfamoilbenzoatos, foram determinados parametros fisico-quimicos obtidos pelo metodo CNDO/2, alguns dos quais, juntamente com a conectividade molecular, permitiram estabelecer os fatores que influem na atividade farmacologica e o possivel mecanismo de acao ao nivel molecular

Motility and drug susceptibility of Angiostrongylus cantonensis developing from gamma-irradiated first-stage larvae.

The effects of neuropharmacological agents on the motility of irradiated and non-irradiated Angiostrongylus cantonensis adult females were studied. GABA induced complete paralysis in non-irradiated and 5,000 R-irradiated worms, but caused only slight paralysis on 10,000 R-irradiated worms. The paralytic effect of GABA was antagonised by picrotoxin. The reason for low susceptibility of heavily irradiated worms to GABA is not known. There was no difference in susceptibility of non-irradiated and irradiated worms to other neuropharmacological agents including eserine, phenylephrine and dibenamine.

Efeitos do alfatesin sobre a atividade convulsivante da estricnina e do pentetrazol em coelhos / Effects of alphatesin on the convulsive activity of the strichinin and pentetrazol in rabbits

O uso de Alfatesin é acompanhado com freqüência de fenômenos excitatórios de natureza ainda näo esclarecida apesar de ser empregado, eventualmente, em crises de epilepsias. Por esse motivo resolvemos estudar os efeitos desse agente, isoladamente (0,1 kg1) e em associaçäo com pentetrazol (10 mg. kg-1) ou 0,1 ml de estricnina (0,2 mg.kg-1) por via venosa, em dez coelhos. As drogas foram utilizadas isoladamente e em associaçäo nos mesmos animais, em intervalos de quatro dias. Foram observadas: presença de reflexo córneo palpebral e de endireitamento, nistagmo, miose, tono muscular, ataxia, analgesia e convulsäo. A cada atributo foi conferida uma nota de 0 a 3, de acordo com a sua intensidade. Foi observado que o alfatesin, isoladamente, determina sedaçäo, hipotonia muscular, ataxia e perda do reflexo de endireitamento, mas näo induz analgesia. Associado ao pentetrazol e a estricnina reduz ou abole as manifestaçöes de estimulaçäo do sistema nervoso central características dessas drogas. Ainda é capaz de impedir o óbito induzido pela estricnina isoladamente. A explicaçäo para esses efeitos é discutida, necessitando de estudos mais sofisticados para seu esclarecimento

Hipotese sobre o mecanismo de acao da homeopatia em funcao das recentes contribuicoes produzidas pela neurofisiologia / Hipothesys about the homeopathy action mode in view of the recent neurophysiology contributions

A evolucao das tecnicas de investigacoes biologicas permite apos alguns anos, a fisiologia, estudar as engrenagens mais delicadas celulares e sub-celulares. A este nivel, certos mecanismos de acao bem postos recentemente em evidencia pela neurofisiologia, permite entrever o mecanismo intimo de acao da homeopatia. Nos tomamos como exemplo a acao das doses homeopaticas do OPIUM e do STRYCHNINUM, comparando-as as recentes descobertas concernentes aos sistemas de neuromediacao endorfinica e glicinergica

The Effect of Strychnine on Membrane Properties of Spinal Motoneurons in the Cat

Strychnine (Stry.) has been used, as an instrument for studies of experimental epilepsy, though its precise mode of action has remained obscure. One mechanism of action was partially clarified in 1954 ,by the demonstration that subconvulsive doses of Stry. reduce the amplitude of inhibitory postsynaptic potentials (IPSPs) in the cat's spinal motoneurons (MN). Because of the rapid onset of its action and the absence of effects upon monosynaptic excitatory postsynaptic potentials (EPSPs), it was proposed that Stry. competed with some unidentified transmitter for inhibitory receptor sites on the postsynaptic membrane. Electrophoresis of Stry. is known to block the inhibitory effects of glycine, a likely candidate as an inhibitory transmitter on MN in the cat spinal cord. A Stry. resistant inhibition seems to exist not only in the higher portion of the CNS, but also for the spinal MN. Gamma amino butyric acid (GABA) is a candidate for this synaptic transmitter. In Nembutal anesthetized cat, intracellular recording of spinal MN was performed during Stry. induced seizure. To conclude, it can be said that there were no consistant changes in the MN action potential which would reflect an action of Stry. upon MN's membrane properties important to seizure generation. It is still to be resolved whether the increase in polysynaptic EPSP amplitude is due to a Stry. effect upon the membrane properties of excitatory interneurons or to an effect only upon the inhibitory as well as the EPSPs.