The presynaptic modulation of corticostriatal afferents by mu-opioids is mediated by K+ conductances.
Population spikes associated with the paired pulse ratio protocol were used to measure the presynaptic inhibition of corticostriatal transmission caused by mu-opioid receptor activation. A 1 microM of [D-Ala(2), N-MePhe(4), Gly-ol(5)]-enkephalin (DAMGO), a selective mu-opioid receptor agonist, enhanced paired pulse facilitation by 44+/-8%. This effect was completely blocked by 2 nM of the selective mu-receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-NH (CTOP). Antagonists of N- and P/Q-type Ca(2+) channels inhibited, whereas antagonists of potassium channels enhanced, synaptic transmission. A 1 microM of omega-conotoxin GVIA, a blocker of N-type Ca(2+) channels, had no effect on the action of DAMGO, but 400 nM omega-agatoxin TK, a blocker of P/Q-type Ca(2+)-channels, partially blocked the action of this opioid. However, 5 mM Cs(2+) and 400 microM Ba(2+), unselective antagonists of potassium conductances, completely prevented the action of DAMGO on corticostriatal transmission. These data suggest that presynaptic inhibition of corticostriatal afferents by mu-opioids is mediated by the modulation of K(+) conductances in corticostriatal afferents.
Barral
Jaime
J
Neurociencias, FES Iztacala, UNAM, México City DF 94510, Mexico.
Mendoza
Ernesto
E
Galarraga
Elvira
E
Bargas
José
J
D000344:Afferent Pathways / Q000187:drug effects; D060848:Agatoxins; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D002586:Cesium / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013111:Spider Venoms / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
D060848:Agatoxins; D000701:Analgesics, Opioid; D015220:Calcium Channels; D015221:Potassium Channels; D017450:Receptors, Opioid, mu; D013111:Spider Venoms; C083855:omega-agatoxin-Aa4b; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D002586:Cesium; D001464:Barium; D013004:Somatostatin