Intracellular recording from pyramidal neurones in the in vitro transverse hippocampal slice [proceedings].
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Action Potentials↗
Biomedical subjects
R Dingledine
Publications and source records attributed to R Dingledine.
Inhibitory effects of acetylcholine on neurones in the feline nucleus reticularis thalami.
1. Short iontophoretic pulses of acetylcholine (ACh) inhibited almost every spontaneously active cell encountered in the nucleus reticularis thalami of cats anaesthetized with a mixture of halothane, nitrous oxide and oxygen. On 200 cells the mean current needed to eject an effective inhibitory dose of ACh was 67 +/- 2 nA. When the ACh-evoked inhibition was mimicked by gamma-aminobutyric acid (GABA) or glycine on the same cell, the current required to release ACh was found to be approximately twice as great as that required to release an equally effective dose of GABA or glycine. 2. ACh inhibitions developed with a latency which was very much shorter than that for ACh excitation in cells of the ventrobasal complex. The latency of the ACh-evoked inhibition was as rapid as the onset and offset of the excitation of the same cells glutamate and their inhibition by GABA or glycine. 3. The firing pattern of ACh-inhibited neurones in the nucleus reticularis was characterized by periods of prolonged, high frequency bursts, and their mean firing frequency was 22 Hz. Raster dot displays and interspike interval histograms showed that whereas ACh suppressed the spikes that occurred between bursts much more readily than those that occurred during bursts, all spikes were equally sensitive to the depressant action of GABA and glycine. Large doses of ACh provoked or exaggerated burst activity. 4. ACh-evoked inhibition was extremely sensitive to blockade by short iontophoretic applications of atropine, which had no effect on the inhibitions evoked on the same cell equipotent doses of GABA or glycine. The ACh-evoked inhibitions were also antagonized by dihydro-beta-erythroidine released with slightly larger currents. When tested on the same cell, small iontophoretic applications of picrotoxin and bicuculline methoiodide blocked the inhibition evoked by GABA but had no effect on that evoked by ACh. Iontophoretic strychnine only rarely affected the inhibition evoked by ACh, while readily blocking the inhibition evoked on the same cell by an equipotent dose of glycine. In two cats, intravenous strychnine (1-2 mg/kg) had no effect on the ACh-evoked inhibition, while greatly reducing the sensitivity of the cell under study to glycine. 5. Only four out of forty-eight ACh-inhibted cells tested were inhibited by iontophoretic applications of either guanosine or adenosine 3':5'-phosphate. 6. Cells of the nucleus reticularis have been shown to have an inhibitory action on the thalamic relay cells, which are excited by ACh. It is suggested that the presence of both ACh excited and inhibited cells in different nuclei of the thalamus could be of considerable functional significance in gating sensory transmission through the thalamus.
Acetylcholine↗
Effect of synaptic transmission blockade on morphine action in the guinea-pig myenteric plexus.
Morphine, which inhibits release of acetylcholine from neurons in the myenteric plexus, also inhibits the spontaneous electrical activity of some myenteric neurons. To determine whether morphine acts at a site presynaptic to these neurons, we investigated this morphine effect under conditions of synaptic transmission blockade. Synaptically driven action potentials evoked by point stimulation were recorded extracellularly, and it was shown that all synaptic responses were eliminated or greatly reduced in Ca-free, high-Mg Ringer's with ethylenebis [(oxyethylenenitrilo)]-tetraacetic acid (EGTA), suggesting that synaptic transmission was blocked. Under these conditions, the ability of morphine to inhibit spontaneous electrical activity was virtually unimpaired. Assuming a single locus of narcotic action in the myenteric plexus, it is unlikely, therefore, that the primary action of opiates is to stimulate release of an inhibitory transmitter, to prevent release of an excitatory transmitter or to block the postsynaptic receptor for an excitatory transmitter. Rather, opiates may raise the membrane threshold of a class of neurons. Electric field stimulation activates myenteric neurons, resulting in a morphine-sensitive release of acetylcholine and a contraction of the longitudinal muscle. The ability of field stimulation to induce contractions and of morphine to inhibit these contractions, was virtually unchanged when the only two known excitatory inputs to the cholinergic motor neuron were eliminated by receptor blockade. These observations, taken together, suggest that opiates act directly on the cholinergic motor neuron of the myenteric plexus.
Animals↗
Evidence for naloxone and opiates as GABA antagonists [proceedings].
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Aminobutyrates↗
Single neuron studies of opiate action in the guinea pig myenteric plexus.
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Animals↗
Effects of narcotic opiates and serotonin on the electrical behavior of neurons in the guinea pig myenteric plexus.
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Acetylcholine↗
Lethality of the morphinan isomers levorphanol and dextrorphan.
Significantly different (P<0.05) LD(50) values were found in Swiss-Webster mice for levorphanol (73 mg/kg, i.p.) and dextrorphan (120 mg/kg, i.p.). A subcutaneous injection of naloxone 15 min before challenge prevented the lethal effect of an LD(98) of levorphanol, with ED(50) value of 1.36 mg/kg. Naloxone, in doses from 2 to 100 mg/kg, did not prevent death caused by 150 mg/kg of either dextrorphan or levorphanol. Levorphanol was lethal for mice pretreated with 10 mg/kg of naloxone, a dose sufficient to block opiate-specific lethal effects, but the LD(50) value was 109 mg/kg, in contrast to 73 mg/kg in the absence of naloxone. By the criteria of stereospecificity and naloxone blockade, levorphanol-induced mortality in mice is a typical opiate effect in the lower of the two dose ranges studied. At higher doses of levorphanol a non-specific effect supervenes, with an LD(50) value virtually the same as that of dextrorphan.
Animals↗
Opioid pharmacology in the rat hippocampal slice.
The ability of several opioids in potentiating the synaptic activation of CA1 pyramidal cells in the rat hippocampal slice were compared. Morphine and the opioid peptides, (D-ala2, D-leu5)-enkephalin (DADL), morphiceptin, beta-endorphin, and Tyr-D-Ser-Gly-Phe-Leu-Thr (DSThr) caused a concentration-dependent, naloxone-reversible shift to the left in the input-output (IO) curve constructed by plotting the population spike as a function of the field EPSP. These opioids then produced an increase in the size of the population spike while leaving the EPSP unaffected. In contrast, the kappa agonist prototype, ethylketazocine, had no effect on the IO curve when perfused in concentrations up to 10 microM. The rank order of potency for the opioids in the CA1 region of the hippocampus was DADL greater than DSThr greater than beta-endorphin greater than morphiceptin greater than morphine much greater than ethylketazocine. Thus, opioids that are more specific for delta opiate receptors were the most potent and mu receptor agonists, the least potent in this action. Taken together with previous studies suggesting that morphine and DADL may interact with a common opiate receptor in the CA1 region, the results are consistent with the notion that these epileptiform effects may be primarily mediated by delta opiate receptors in this area although the potency of morphiceptin indicates that mu receptors play some role in this effect.
Analgesics, Opioid↗