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Biomedical subjects

D Lodge

Publications and source records attributed to D Lodge.

At least 163 records · Page 9Linked to original sources

The sensitivity of rat spinal interneurones and renshaw cells to L-glutamate and L-aspartate.

L-Glutamate and L-aspartate were administered electrophoretically near spinal interneurones and Renshaw cells of pentobarbitone-annaesthetized rats. Other spinal interneurones were consistently more sensitive to L-glutamate than to L-aspartate. Renshaw cells, however, showed no consistent difference in their sensitivity to these two amino acids. The results, which are compared with those reported previously in the cat, support the hypothesis that L-glutamate could be a transmitter at spinal primary afferent terminals.

Action Potentials↗

The in vivo inactivation of GABA and other inhibitory amino acids in the cat nervous system.

In cats anaesthetised with pentobarbitone, the effect of inhibitors of the in vitro cellular uptake of GABA were tested on the responses of single central neurones to GABA and other depressant amino acids. (4)- AND (-)-nepecotic acid, (4)-2,4-diaminobutyric acid (DABA) and 2,2-dimethyl-beta-alanine, enhanced the action of GABA on spinal, cerebellar and cerebral cortical neurones. In the spinal cord DABA, and to a less estent (-)-nipecotic acid, enhanced the action of beta-alanine, whereas the actions of glycine and taurine were unaffected by DABA and reduced by (-)-nipecotic acid. In the cerebellum and cerebral cortex, these two substances enhanced the action of GABA, usually to a greater extent than that of beta-alanine and taurine, although this specificity was not marked. The GABA-mediated basket cell inhibition of Purkinje cells in the cerebellum was unaffected by DABA and (-)-nipecotic acid, and neither substance appears suitable for determining the role of uptake processes in the inactivation of synapitcally released GABA. Quantitatively these in vivo results agree more closely with recent vitro uptake studies in cat tissue than the previously published data on rat cerebral cortex and dorsal root ganglia, and the observations provide further evidence for the importance of cellular uptake in maintaining low extraneuronal concentrations of inhibitory amino acid transmitters.

Action Potentials↗

Studies on field potentials and on single cells in the inferior olivary complex of the rat.

Field and unitary action potentials have been recorded in the inferior olivary complex of pentobarbital anaesthetized rats. Spontaneous and antidromically evoked unitary potentials, and antidromically evoked field potentials all showed the same biphasic profile. Repetitive antidromic stimulation resulted in attenuation of the field potential with stimulation frequencies as low as 10 Hz. The latency of juxtafastigially evoked spikes was variable, and decreased with increasing stimulus strengths. Electrophoretically applied glycine, gamma-aminobutyric acid, noradrenaline, dopamine and 5-hydroxytyptamine all reduced the amplitude of the antidromic potential, but sometimes caused a transient increase preceding this decrease. Orthodromically (femoral nerve) evoked potentials were different in form and could assume one of two distinct profiles. The effects of electrophoretically applied DL-homocysteate (DLH) and the putative transmitters listed above on the form of such field potentials are described. DLH, ACh and 5-HT were tested on single olivary neurones, which had spontaneous firing rates of less than 2 Hz. These compounds had only slight effects on firing rates although marked changes were seen in action potential configuration. Spontaneous synchronous discharges of groups of olivary neurones are described. This and other findings confirm that olivary units have a tendency to both rhythmical and synchronous firing.

Action Potentials↗

Drug-induced rhythmical activity in the inferior olivary complex of the rat.

Experiments have been performed on pentobarbitone anesthetized or decerebrated rats. The nature of the synchronous rhythmical activity which occurs in the inferior olive following the electrophoretic or systemic administration of harmaline, harmine, dihydro-beta-erythroidine and various other compounds, is described. Harmine was shown to reduce the late phase of biphasic unitary action potentials and to evoke massed synchronous rhythmical activity on which the units were superimposed. The beta-carboline was more effective than ACh or DL-homocysteate (DLH) in increasing cell discharge rates. Synchronized rhythmical activity was recorded more than 500 mum from the site of ejection of the rhythm-inducing drugs. Developed rhythmical activity reduced the size of antidromic field potentials, but antidromic invasion could reset the rhythm of submaximal rhythmical activity. The effects of ACh and DLH, glycine, GABA, NA, DA and 5-HT were tested on established rhythmical activity. Of these, 5-HT was the only compound which almost invariably antagonized the rhythm. A number of tryptamine derivatives and reported 5-HT antagonists, as well as parachlorophenylalanine, have been tested, but the results were largely inconclusive. The hypothesis is advanced that the drug-induced rhythm results from the inhibition of a tonic inhibitory serotonergic input. This antagonism releases an innate tendency of olivary cells to discharge both rhythmically and synchronously.

Acetylcholine↗

The effects of beta-carbolines on responses to acetylcholine, noradrenaline, 5-hydroxytryptamine and amino acids in the rat spinal cord.

Various drugs have been applied electrophoretically to Renshaw cells and to unidentified spinal neurones in pentabarbitone anaesthetized or decerebrated rats. Responses to noradrenaline (NA) and 5-hydroxytryptamine (5-HT) have not previously been described at this site and were of two types; either monophasic depression or biphasic depression-excitation. The effect of harmine on these responses was examined. Harmine and harmaline were also tested on the excitant responses to acetylcholine (ACh) and DL-homocysteate (DLH), and on the depressant responses to glycine and gamma-aminobutyric acid (GABA). On some cells harmaline antagonized ACh, but not DLH, and glycine, but not GABA, responses. Harmine caused only non-specific depression and spike configuration changes. The effects of harmine on NA and 5-HT responses were usually non-specific, and any anatagonism was usually accompanied by, or soon followed by spike changes. LSD was also tested on the amine responses. LSD itself had a clear depressant effect on neuronal firing rates. It could either antagonize or potentiate NA and 5-HT depressant responses, but the antagonism in particular was closely followed by spike changes. Somewhat more specific antagonism of the late excitation was seen.

Acetylcholine↗

Benzodiazepines and central glycine receptors.

1 In cats, anaesthetized with pentobarbitone, intravenous diazepam (minimum dose 3.0 mg/kg) enhanced dorsal root potentials but did not significantly diminish the reduction by electrophoretic strychnine of the inhibitory action of electrophoretic glycine on dorsal horn interneurones. 2 In mice, intraperitoneal diazepam (2.5 mg/kg) had no appreciable effect on the potency of strychnine as a convulsant, although providing some protection against bicuculline. 3 These observations, together with the failure of chlordiazepoxide to either inhibit the firing of spinal interneurones or reduce antagonism between strychnine and glycine when administered locally, provide no support for the interaction between benzodiazepines and mammalian central glycine receptors which has been proposed on the basis of in vitro studies of strychnine binding.

Action Potentials↗

A pharmacological study of Renshaw cell inhibition.

1. In cats anaesthetized with pentobarbitone a pharmacological investigation was made of the inhibition of Renshaw cells by dorsal root afferent volleys and ventral root antidromic volleys, and of the inhibition of motoneurones by Renshaw cells. 2. The effects of strychnine, bicuculline and tetanus toxin indicate that both glycine and GABA operate as inhibitory transmitters released on Renshaw cells by dorsal root volleys. 3. The 'mutual' inhibition of Renshaw cells, and the recurrent inhibition of motoneurones by Renshaw cells, are suppressed by strychnine: Renshaw cells are thus glycinergic inhibitory neurones, a proposal consistant with recent evidence for strychnine-sensitive inhibition of Ia interneurones by Renshaw cells. 4. The 'pause' which follows high frequency synaptic excitation of Renshaw cells is insensitive to strychnine, bicuculline and tetanus toxin, and is considered unlikely to be the consequence of synaptic inhibition.

Action Potentials↗

The pharmacology of the inhibition of dorsal horn neurones by impulses in myelinated cutaneous afferents in the cat.

The effects of microelectrophoretic strychnine and bicuculline methochloride were studied on the time course of synaptic inhibitions of single dorsal horn neurones in the lumbar spinal cord of cats anaesthetized with pentobarbitone. The inhibitions, evoked by volleys in mixed myelinated cutaneous afferents, varied in latency and duration. In general, early inhibitions (latency less than 12msec; duration less than 36 msec) were reduced by microelectrophoretic strychnine whereas late inhibitions (latency more than 16 msec and more prolonged in duration) were usually sensitive to bicuculline. These results can be interpreted in terms of glycine and GABA as the inh ibitory transmitters of early and late inhibitions respectively.

Animals↗

Acetylcholine receptors on Renshaw cells of the rat.

Experiments have been performed on Renshaw cells of rats to investigate the receptors mediating both the responses to electrophoretically applied cholinergic excitants and the synaptic excitation following stimulation of the ventral roots. The effects of atropine and dihydro-beta-erythroidine, muscarinic and nicotinic antagonists respectively, have been tested on both types of excitation. Most importantly we found that in the rat the ventral root evoked response can be blocked by atropine as well as by DHbetaE. It was not possible to categorise the responses to the cholinergic agents in terms of muscarinic and nicotinic receptors. In addition we have failed the late (muscarinic) excitation seen in the cat.

Acetylcholine↗

Acetylcholine-sensitive cells in the caudal medulla of the rat: distribution, pharmacology and effects of pentobarbitone.

1. The distribution of cholinoceptive and non-cholinoceptive cells in various nuclei of the caudal medulla of the rat is described. 2. The nature of the responses of cells of the paramedian reticular nucleus and of the perihypoglossal nuclei to electrophoretically applied acetylcholine (ACh) was investigated. 3. In unanaesthetized decerebrate preparations ACh responses were usually of a "fast onset-fast offset" nature. Dihydro-beta-erythroidine was a more effective antagonist than atropine. 4. In rats anaesthetized with barbiturate nearly all the tach responses showed a slower onset and prolonged action. Atropine was the more effective antagonist. 5. The synaptic responses of cells of the paramedian reticular and perihypoglossal nuclei to stimulation of glossopharyngeal, superior laryngeal, lingual and hypoglossal nerves were investigated. It is concluded that ACh does not mediate the responses at the level of these nuclei.

Acetylcholine↗