Actions of opioids on excitatory and inhibitory transmission in substantia gelatinosa of adult rat spinal cord.
1. The actions of opioid receptor agonists on synaptic transmission in substantia gelatinosa (SG) neurones in adult (6- to 10-week-old) rat spinal cord slices were examined by use of the blind whole-cell patch-clamp technique. 2. Both the mu-receptor agonist DAMGO (1 microM) and the delta-receptor agonist DPDPE (1 microM) reduced the amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) which were monosynaptically evoked by stimulating Adelta afferent fibres. Both also decreased the frequency of miniature EPSCs without affecting their amplitude. 3. In contrast, the kappa-receptor agonist U-69593 (1 microM) had little effect on the evoked and miniature EPSCs. 4. The effects of DAMGO and DPDPE were not seen in the presence of the mu-receptor antagonist CTAP (1 microM) and the delta-receptor antagonist naltrindole (1 microM), respectively. 5. Neither DAMGO nor DPDPE at 1 microM affected the responses of SG neurones to bath-applied AMPA (10 microM). 6. Evoked and miniature inhibitory postsynaptic currents (IPSCs), mediated by either the GABAA or the glycine receptor, were unaffected by the mu-, delta- and kappa-receptor agonists. Similar results were also obtained in SG neurones in young adult (3- to 4-week-old) rat spinal cord slices. 7. These results indicate that opioids suppress excitatory but not inhibitory synaptic transmission, possibly through the activation of mu- and delta- but not kappa-receptors in adult rat spinal cord SG neurones; these actions are presynaptic in origin. Such an action of opioids may be a possible mechanism for the antinociception produced by their intrathecal administration.
Department of Physiology, Saga Medical School, Saga 849-8501, Japan.
T
T
Kohno
E
E
Kumamoto
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H
Higashi
K
K
Shimoji
M
M
Yoshimura
D000818:Animals; D044482:Benzeneacetamides; D004558:Electric Stimulation; D004594:Electrophysiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018847:Opioid Peptides / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013376:Substantia Gelatinosa / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D044482:Benzeneacetamides; D004745:Enkephalins; D018847:Opioid Peptides; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; C045444:U 69593