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

Abstract

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 ∼90% by SB-334867 (OX 1-receptor antagonist) (10 μM) but not naloxone (10 μM). [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 μM [41.8%] and 4.3 μM [54.9%] respectively. The effects of DAMGO and spiradoline were naloxone (10 μM)-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.