Lack of an interaction between orexinergic and opioid/nociceptinergic systems in rat cerebrocortical slices

We have recently reported that orexins (OXs) selectively evoke norepinephrine release from rat cerebrocortical slices. In the present study, we have examined orexin-opioid interactions in OXA (100 nM) and K(+) (40 mM)-evoked norepinephrine release. OXA-evoked norepinephrine release was reversed approximately 90% by SB-334867 (OX(1)-receptor antagonist) (10 microM) but not naloxone (10 microM). [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE) (DOP-agonist) and nociceptin/orphanin-FQ (N/OFQ) also failed to affect OXA-evoked release. [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) (MOP-agonist) and spiradoline (KOP-agonist) significantly reduced OXA-evoked release with the concentration producing 50% of the maximal inhibition (EC(50)) [maximal inhibition (E(max))] of 3.2 microM [41.8%] and 4.3 microM [54.9%] respectively. The effects of DAMGO and spiradoline were naloxone (10 microM)-insensitive. In contrast, naloxone significantly antagonized the inhibitory effects of DAMGO and spiradoline on K(+)-evoked release. We conclude that opioid receptors (DOP and KOP) are involved in K(+) but not OXA-evoked release. Moreover, we have failed to demonstrate an interaction between orexinergic and opioid/N/OFQ-ergic systems in this system.