Effects Of Bicuculline Research Articles

Effects of bicuculline on functions of inhibition in visual cortex.

FURTHER to a recent report1 on the effects of intravenous bicuculline on neurones in the cat visual cortex, we feel that we should present some preliminary results from our own experiments.

Bicuculline and picrotoxin as antagonists of γ-aminobutyrate and neuromuscular inhibition in the lobster

Bicuculline at 2 × 10 −4 M has a small but consisten antagonisctic effect on neurally-evoked neuromuscular inhibition in the lobster. This drug similarly antagonized the action of exogenously applied GABA. Picrotoxin at 2 × 10 −6 M had a greater antagonistic effect on both neurally evoked inhibition and the activity of applied GABA. Judging from the effects of bicuculline and picrotoxin on dose-response curves for GABA, the antagonistic properties of the two alkaloids appeared to be different in nature. The action of bicuculline appeared to be non-competitive whereas that of picrotoxin seemed to be more consistent with competitive antagonism. Bicuculline increased the amplitude of excitatory postsynaptic potentials recorded from the muscle fibers. This latter effect may be a consequence of a drug-induced increase in the resistance of the non-synaptic membrane. Hence, in addition to its action on GABA receptors, bicuculline appears to have non-synaptic effects which broaden the interpretation of its pharmacological activity.

Effects of bicuculline on central inhibition

The effects of the specific gamma aminobutyric acid (GABA) antagonist bicuculline were investigated on direct, presynaptic and reticular inhibition and cerebellar disfacilitation of the segmental monosynaptic action potentials of decerebrate cats. Bicuculline markedly suppressed presynaptic inhibition of the quadriceps, posterior bicepssemitendinosus and gastrocnemius-soleus monosynaptic action potentials but had no effect on direct inhibition of these same potentials. Reticular inhibition of the quadriceps potentials was unaltered with bicuculline, but reticular inhibition of the posterior biceps-semitendinosus potentials was significantly suppressed. Cerebellar disfacilitation of both the quadriceps and posterior biceps-semitendinosus potentials was also blocked with bicuculline. The present study supports earlier propositions that GABA may be involved in presynaptic inhibition and cerebellar disfacilitation of the segmental potentials and suggests that reticular inhibition of the posterior biceps-semitendinosus monosynaptic action potentials may also be mediated by GABA.

Electroencephalographic effects of bicuculline

The effects of bicuculline on the electrical activity of various sites of the cerebro-spinal axis have been studied in the rabbit and in the rat. Bicuculline induces electroencephalographic patterns very similar to that of picrotoxin and pentamethylenetetrazol and distinct from that induced by strychnine.

The effects of bicuculline on the isolated spinal cord of the frog

An investigation has been made of the effects of topically applied bicuculline, a reported gamma-aminobutyric acid (GABA) antagonist, on the isolated, hemisected frog spinal cord by recording ventral and dorsal root potentials and reflexes evoked by volleys to various spinal cord inputs. Bicuculline had potent excitatory effects causing depolarization, spontaneous potentials in ventral and dorsal roots, and an increased polysynaptic ventral root reflex. More importantly, the alkaloid blocked presynaptic inhibition of orthodromic reflex activity produced by preceding ventral root stimulation and primary afferent depolarization. These effects were attributed to a demonstrated antagonism of the direct depolarizing effects of GABA on dorsal root terminals by the alkaloid. These actions of bicuculline suggest that GABA may be the transmitter responsible for primary afferent depolarization and presynaptic inhibition in the amphibian.

Effect of bicuculline on the GABA receptor of the crayfish neuromuscular junction.

SINCE it was reported that bicuculline is a specific antagonist of γ-aminobutyric acid (GABA)1–3, much attention has been paid to the action of this alkaloid on cortical neurones4–6. Thus it seemed worthwhile to test the mode of action of bicuculline on the inhibitory neuromuscular junction of the crayfish, where the action of GABA has been well documented7,8.

The effect of bicuculline upon synaptic inhibition in the cerebral and cerebellar cortices of the cat

Summary (1) In cats anaesthetuzed with pentobarbitone sodium a study was made of the action of bicuculline on the synaptic inhibition of Purkinje and pyramidal tract neurones. (2) he inhibition of Purkinje cells by ‘off-line’ electrical stimulation of the surface of the cerebellar cortex was readily blocked by bicuculline administered electrophoretically or intravenously. (3) The inhibition of many pyramidal tract neurones following electrical stimulation of the pyramid or the surface of the cerebral cortex, or by chemical stimulation of intracortical neurones, was reduced by bicuculline, particularly when administered electrophoretically. (4) Since bicuculline is an antagonist of the inhibitory action of GABA upon Purkinje and pyramidal tract neurones, these findings provide decisive pharmacological evidence that the inhibitory basket-type cells of the cerebellar and cerebral cortices release GABA as a transmitter.

Evaluation of bicuculline as a GABA antagonist.

THERE has been controversy recently about the reliability of bicuculline as an antagonist of the putative inhibitory transmitter γ-aminobutyric acid (GABA) in the brain1–3. Although the effects of bicuculline have so far been explained in terms of its combination with the GABA receptor, bicuculline might also affect the removal processes for GABA and the synthesis and release of endogenous GABA. We have therefore made quantitative analyses of the effects of iontophoretically applied bicuculline on the responses of neurones to GABA and have also estimated the effects of bicuculline on the concentration and turnover of GABA in the brain, GABA uptake and the synthetic and degradative enzymes glutamate decarboxylase (GAD) and 4-aminobutyrate : 2-oxoglutarate aminotransferase (GABA-T).

Antagonism between bicuculline and GABA in the cat brain

(1) An investigation was made of the effects of bicuculline on the inhibition by amino acids of neurones in the lateral vestibular nucleus, the ventrobasal thalamus, and the cerebellar, hippocampal and cerebral cortices of cats anaesthetized with pentobarbitone sodium. (2) In all regions, bicuculline reversibly antagonized the action of GABA without modifying that of glycine. In contrast strychnine suppressed the inhibitory effect of glycine but not that of GABA. (3) The inhibition by β-alanine of the firing of thalamic, cerebellar, hippocampal and cerebral cortical neurones was reduced by both bicuculline and strychnine; the inhibition of lateral vestibular neurones by β-alanine, like that of spinal neurones, was insensitive to bicuculline. (4) The classification of depressant amino acids on the basis of antagonism by bicuculline and strychnine is different when these substances are tested on spinal and supraspinal neurones. (5) Concentrations of bicuculline adequate to modify the sensitivity of Purkinje cells to GABA had little or no effect on the inhibition of these neurones by noradrenaline. (6) The relatively high degree of specificity of bicuculline as a GABA antagonist indicates that this alkaloid is of considerable value in determining whether or not a particular inhibitory pathway could operate by releasing GABA as an inhibitory transmitter.

The effect of bicuculline on primary afferent terminal excitability

The effect of bicuculline on primary afferent terminal excitability

Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord of the cat

Summary (1) A study has been made of the effects of bicuculline, a phthalide isoquinoline convulsant alkaloid, on the inhibition of spinal neurones by amino acids and the synaptic inhibition of spinal reflexes in cats anaesthetised with pentobarbitone sodium. (2) The inhibitory effects on spinal neurones of glycine, β-alanine, l -α-alanine, taurine and nor -adrenaline were not affected by electrophoretically administered bicuculline, whereas the alkaloid was a reversible antagonist of the actions of GABA, β-hydroxy-GABA, δ-aminovaleric acid, muscimol and imidazole acetic acid. (3) The classification of amino acids depressing the firing of spinal neurones into ‘glycine-like’ and ‘GABA-like’ is identical when either strychnine or bicuculline is used as an antagonist: strychnine blocks the action of glycine-like amino acids, bicuculline that of GABA-like amino acids. (4) Bicuculline administered intravenously in convulsant doses does not affect the strychnine-sensitive inhibition of spinal motoneurones, but reduces both the prolonged inhibition of these cells which is sensitive to picrotoxin and dorsal root potentials evoked by impulses in cutaneous and muscle afferents. (5) Since GABA has a hyperpolarizing inhibitory transmitter-like action on motoneurones, the proposal is made that this amino acid, released at inhibitory axodendritic or axo-axonic synapses, is responsible for the prolonged inhibition of spinal motoneurones by repetitive impulses in afferent fibres (‘presynaptic’ inhibition). (6) The relationship of primary afferent depolarization to this inhibition is discussed. (7) The effects of laudanosine, gelsemine and dendrobine on spinal neurones resemble that of strychnine.

The effect of bicuculline on the inhibition of mitral cells of the olfactory bulb

In the olfactory bulb, GABAB receptors are selectively located in the glomerular layer. A current hypothesis is that GABAergic inhibition mediated through these receptors would be, at least partly, presynaptic and would exerted by decreasing the release of the olfactory receptor neuron excitatory neurotransmitter. Here, we assessed, in the frog, the in vivo action of baclofen, a GABAB agonist, on single-unit mitral cell activity in response to odors. Local application of baclofen in the glomerular region of the olfactory bulb was shown to drastically affect mitral cell spontaneous activity, since they became totally silent. Moreover, under baclofen, mitral cells still responded to odors and still specified odor concentration increases through their temporal response patterns. The pharmacological specificity of the GABAB agonist action was confirmed by showing that saclofen, a GABAB antagonist, partly prevented the inhibitory action of baclofen and restored the initial rate of mitral cell spontaneous activity.The results show that GABAB-mimicked inhibition suppressed mitral cell spontaneous activity while odor responses were maintained. This suggests that olfactory receptor neurons partly drive spontaneous mitral cell activity. Moreover, the effect of GABAB-mediated inhibition was seen to be very close to that described previously for dopamine D2 receptor-mediated inhibition. In conclusion, we propose that these two inhibitory mechanisms would offer the possibility to reduce or suppress mitral cell spontaneous activity so as to make their responses to odor especially salient.

The effects of bicuculline and GABA on the superior cervical ganglion of the cat

The effects of bicuculline and GABA on the superior cervical ganglion of the cat

Inhibitory of glycine on spinal neurons in the cat.

Inhibitory of glycine on spinal neurons in the cat.

RECURRENT COLLATERAL INHIBITION IN PYRAMIDAL TRACT NEURONS.

RECURRENT COLLATERAL INHIBITION IN PYRAMIDAL TRACT NEURONS.

Observations on the physiological action of strychnine.

ArticlesOBSERVATIONS ON THE PHYSIOLOGICAL ACTION OF STRYCHNINEP. D. Wall, and N. H. HorwitzP. D. Wall, and N. H. HorwitzPublished Online:01 Jul 1951https://doi.org/10.1152/jn.1951.14.4.257MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByComparative neuroanatomy: Integrating classic and modern methods to understand association fibers connecting dorsal and ventral visual cortexNeuroscience Research, Vol. 146Patrick D. WallThe primate temporal pole: its putative role in object recognition and memoryBehavioural Brain Research, Vol. 77, No. 1-2Insula of the old world monkey. II: Afferent cortical input and comments on the claustrumThe Journal of Comparative Neurology, Vol. 212, No. 1Insular interconnections with the amygdala in the rhesus monkeyNeuroscience, Vol. 6, No. 7Cortical and subcortical afferents to the amygdala of the rhesus monkey (Macaca mulatta)Brain Research, Vol. 190, No. 2Convulsant AlkaloidsTHE EFFECT OF BICUCULLINE, METRAZOL, PICROTOXIN AND STRYCHNINE ON THE RELEASE OF [ 3 H]GABA FROM RAT BRAIN SLICESJournal of Neurochemistry, Vol. 18, No. 12Evidence for biogenic amine receptors in toad sciatic nervesInternational Journal of Neuropharmacology, Vol. 8, No. 6ReferencesActa Physiologica Scandinavica, Vol. 49Effects of Strychnine with Special Reference to Spinal Afferent FibresEpilepsia, Vol. C4, No. 1 More from this issue > Volume 14Issue 4July 1951Pages 257-263 https://doi.org/10.1152/jn.1951.14.4.257PubMed14851002History Published online 1 July 1951 Published in print 1 July 1951 Metrics

Limitations of method of strychnine neuronography.

ArticlesLIMITATIONS OF METHOD OF STRYCHNINE NEURONOGRAPHYB. FrankenhaeuserB. FrankenhaeuserPublished Online:01 Jan 1951https://doi.org/10.1152/jn.1951.14.1.73MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByBiological Characteristics of Connection-Wise Resting-State Functional Connectivity Strength21 January 2019 | Cerebral Cortex, Vol. 29, No. 11Comparative neuroanatomy: Integrating classic and modern methods to understand association fibers connecting dorsal and ventral visual cortexNeuroscience Research, Vol. 146An evidence‐based approach to human dermatomesClinical Anatomy, Vol. 21, No. 5Computational analysis of functional connectivity between areas of primate cerebral cortex29 January 2000 | Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, Vol. 355, No. 1393Global relationship between anatomical connectivity and activity propagation in the cerebral cortex29 January 2000 | Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, Vol. 355, No. 1393The primate temporal pole: its putative role in object recognition and memoryBehavioural Brain Research, Vol. 77, No. 1-2Corticofugal actions on the lateral cervical nucleus of the catExperimental Neurology, Vol. 68, No. 3Cortical and subcortical afferents to the amygdala of the rhesus monkey (Macaca mulatta)Brain Research, Vol. 190, No. 2SEIZURE DEVELOPMENT FOLLOWING REPEATED ELECTRICAL STIMULATION OF CENTRAL OLFACTORY STRUCTURESAnnals of the New York Academy of Sciences, Vol. 290, No. 1 Tonic FunctioConvulsant AlkaloidsGenesis of epileptic interictal spikes. New knowledge of cortical feedback systems suggests a neurophysiological explanation of brief paroxysmsBrain Research, Vol. 52THE EFFECT OF BICUCULLINE, METRAZOL, PICROTOXIN AND STRYCHNINE ON THE RELEASE OF [ 3 H]GABA FROM RAT BRAIN SLICESJournal of Neurochemistry, Vol. 18, No. 12ReferencesStrychnine reversal of inhibitory potentials in pyramidal tract neuronesInternational Journal of Neuropharmacology, Vol. 4, No. 3REFERENCESReferencesActa Physiologica Scandinavica, Vol. 49Effects of Strychnine with Special Reference to Spinal Afferent FibresEpilepsia, Vol. C4, No. 1The neuroanatomical basis for clinical neurology. By Talmadge L. Peele M.D. McGraw-HILL Book Company, Inc., New York, Toronto, London. 1954. Price $12.50. 564 pp.The Journal of Comparative Neurology, Vol. 102, No. 3Reproduction of the 3 per Second Spike and Wave EEG Pattern by Snbcortical Electrical Stimulation in CatsActa Physiologica Scandinavica, Vol. 33, No. 2-3Cortico-thalamic connections from gyrus proreus and first and second somatic sensory areas of the catThe Journal of Comparative Neurology, Vol. 100, No. 1Die Tätigkeit des NervensystemsSTRYCHNINE NEURONOGRAPHY OF THE STRIATE NUCLEI IN CAT'S BRAINPsychiatry and Clinical Neurosciences, Vol. 5, No. 2 More from this issue > Volume 14Issue 1January 1951Pages 73-79 https://doi.org/10.1152/jn.1951.14.1.73PubMed14784875History Published online 1 January 1951 Published in print 1 January 1951 Metrics