Cellular actions of opioids on periaqueductal grey neurons from C57B16/J mice and mutant mice lacking MOR-1.
1 Patch clamp recordings were made from periaqueductal grey (PAG) neurons in vitro to investigate the cellular actions of opioids in wild-type C57B16/J mice and mutant mice lacking the first exon of the micro -opioid (MOP) receptor. 2 In wild-type mice, the kappa-(KOP) agonist U-69593 (300 nM) and the mixed micro /delta-opioid agonist met-enkephalin (10 micro M), but not the delta-(DOP) agonist deltorphin (300 nM), reduced the amplitude of evoked GABA(A)-mediated inhibitory postsynaptic currents (IPSCs). Met-enkephalin and U-69593 also reduced the rate of spontaneous miniature IPSCs, but had no effect on their amplitude and kinetics. In micro -receptor-deleted mice, only U-69593 (300 nM) reduced the amplitude of evoked IPSCs. 3 In wild-type mice, the MOP agonist DAMGO (3 micro M) produced an outward current in 76% of the neurons. Deltorphin and U-69593 produced outward currents in 24 and 32% of the neurons, respectively. In micro -receptor-deleted mice, deltorphin and U-69593 produced similar outward currents in 32 and 27% of the neurons, respectively, while DAMGO was without effect. All neurons in both the wild-type and micro -receptor-deleted mice responded with similar outward currents to either the GABA(B) receptor agonist baclofen (10 micro M), or the opioid-like receptor ORL1 (NOP) agonist nociceptin (300 nM). 4 The DAMGO-, deltorphin-, U-69593-, baclofen- and nociceptin-induced currents displayed inward rectification and reversed polarity at -109 to -116 mV. 5 These findings indicate that micro -, delta- and kappa-opioid receptor activation has complex pre- and postsynaptic actions within the mouse PAG. This differs to the rat PAG where only micro -opioid receptor actions have been observed.
Vaughan
Christopher W
CW
Pain Management Research Institute, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia. chrisv@med.usyd.edu.au
Bagley
Elena E
EE
Drew
Geoffrey M
GM
Schuller
Alwin
A
Pintar
John E
JE
Hack
Stephen P
SP
Christie
MacDonald J
MJ
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000494:pharmacology; D005260:Female; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000235:genetics / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000701:Analgesics, Opioid; D044482:Benzeneacetamides; D058787:GABA-A Receptor Antagonists; D009842:Oligopeptides; D024661:Potassium Channels, Inwardly Rectifying; D011759:Pyrrolidines; D011963:Receptors, GABA-A; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C059567:deltorphin; D004744:Enkephalin, Methionine; C045444:U 69593