“…This change, which was seen within 25-60 min of a change to Mg2+-free medium, paralleled changes in the response to NMA (see Fig. 4 (Anis, Burton, Berry & Lodge, 1983) in eight experiments (twenty neurones), cyclazocine (Berry, Dawkins & Lodge, 1984) in six (fifteen neurones) and APV in nine (twenty-eight neurones).…”
SUMMARY1. In isolated slices of rat cerebral cortex, intracellular recordings were obtained from pyramidal cells that were predominantly in layers II/III. These cells could be antidromically activated from the underlying white matter and had resting potentials of > -75 mV, action potentials with amplitudes of > 70 mV (measured from threshold), overshoots of 20-30 mV, and thresholds 20-30 mV positive to the resting potential.2. The responses of these cells to short (1-2 s) pulses of electrophoretically applied N-methylaspartate (NMA) decreased in amplitude with membrane hyperpolarization between -40 and -120 mV, and were associated with an apparent increase in membrane resistance when recorded in the presence of 1 mMMg2+. However, in the absence of Mg2+, responses to NMA increased progressively in amplitude with hyperpolarization and were associated with a decrease in membrane resistance.
“…This change, which was seen within 25-60 min of a change to Mg2+-free medium, paralleled changes in the response to NMA (see Fig. 4 (Anis, Burton, Berry & Lodge, 1983) in eight experiments (twenty neurones), cyclazocine (Berry, Dawkins & Lodge, 1984) in six (fifteen neurones) and APV in nine (twenty-eight neurones).…”
SUMMARY1. In isolated slices of rat cerebral cortex, intracellular recordings were obtained from pyramidal cells that were predominantly in layers II/III. These cells could be antidromically activated from the underlying white matter and had resting potentials of > -75 mV, action potentials with amplitudes of > 70 mV (measured from threshold), overshoots of 20-30 mV, and thresholds 20-30 mV positive to the resting potential.2. The responses of these cells to short (1-2 s) pulses of electrophoretically applied N-methylaspartate (NMA) decreased in amplitude with membrane hyperpolarization between -40 and -120 mV, and were associated with an apparent increase in membrane resistance when recorded in the presence of 1 mMMg2+. However, in the absence of Mg2+, responses to NMA increased progressively in amplitude with hyperpolarization and were associated with a decrease in membrane resistance.
“…Others have noted that NAM and PCP can inhibit dorsal horn intemeurons (Anis et al, 1983;Berry et al, 1984), and (T binding sites have been demonstrated in the spinal cord (Quirion et al, 198 1;Zukin, 1979, 1981). NAM is a weak analgesic (Martin et al, 1976), but PCP and the related compound, ketamine, are anesthetics.…”
The effects of iontophoretically applied opiates were tested on 24 spinothalamic tract cells in 12 anesthetized monkeys. The drugs used were chosen because of their agonist actions on different classes of opiate receptors (mu, morphine; kappa, dynorphin; delta, methionine enkephalinamide; sigma, N-allylnormetazocine or SKF 10047 and phencyclidine). The actions of the opiate drugs were generally inhibitory, although excitatory or mixed effects were sometimes seen, especially with morphine and dynorphin. Drug effects could change, depending on the position of the iontophoretic electrode array or on the current employed. Naloxone sometimes antagonized the action of the opiate drugs used, but naloxone did not seem to be a drug suited for iontophoretic application. A number of explanations are discussed to explain the variable actions of the opiate drugs.
“…However, recent radioligand binding studies using the prototypical a ligand, [3H]-( + )-NANM, have demonstrated that (+ )-NANM labels two distinct recognition sites in cerebral membranes: a high affinity site sensitive to nanomolar concentrations of haloperidol and a lower affinity site which corresponds to the recognition site labelled by [3H]-PCP (Zukin & Zukin, 1979;Vincent et al, 1979;Su, 1982;Tam, 1983;Largent et al, 1984;Martin et al, 1984). However, both the benzomorphans and the arylcyclohexylamines are also non-competitive antagonists of the N-methyl-D-aspartic acid (NMDA) receptor (Anis et al, 1983;Berry et al, 1984) and it is not clear which of these properties mediate their psychotomimetic effects.…”
1 The involvement of the haloperidol-sensitive, a recognition site and the N-methyl-D-aspartic acid (NMDA) receptor in the mediation of the discriminative stimulus properties of (+)-N-allylnormetazocine ((+)-NANM, (+)-SKF 10,047), has been investigated in the rat by use of a two-lever, operant drug discrimination paradigm.2 Six compounds with nanamolar affinity for the a recognition site ((±)-pentazocine, (+)-3-(hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP), ditolylguanidine (DTG), haloperidol, (-)-butaclamol and BMY 14802) were investigated for their ability to generalise or antagonise the (+)-NANM discriminative stimulus. Each drug was tested at doses found in an ex vivo radioligand binding assay to displace [3H]-DTG from the central a recognition site by more than 40%. 3 While (±)-pentazocine (in the presence of naloxone) generalised and (+)-3-PPP partially antagonised the (+)-NANM cue, the other putative a ligands were ineffective either as agonists or antagonists at doses clearly occupying the a site in vivo. 4 Dose-dependent generalisation to the (+)-NANM cue was seen with the selective non-competitive NMDA receptor antagonist, MK-801, a compound devoid of significant affinity for the a recognition site. 5 (±)-Pentazocine was found to antagonise seizures induced in the mouse by NMDLA, a model reflecting antagonism of central NMDA receptors, and a strong correlation was found between the rank order of potency of compounds to generalise to the (+)-NANM discriminative stimulus and their potencies as anticonvulsants. 6 In conclusion, no evidence was found to substantiate the contention that the discriminative stimulus properties of (+)-NANM are mediated by the haloperidol-sensitive a recognition site. On the other hand, the results are consistent with the interoceptive stimulus being mechanistically based in the NMDA receptor complex.
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