Lack of interaction between orexinergic and α2-adrenergic neuronal systems in rat cerebrocortical slices

Orexinergic and norepinephrinergic α2-adrenoceptor expressing neurons contribute to the regulation of the sleep-wakefulness cycle. In the present study, we have examined a possible interaction between orexinergic and α2-adrenergic systems in orexin-A (100 nM)- and K+ (25 mM)-evoked norepinephrine release from slices of rat cerebrocortex. In this tissue norepinephrinergic neurons are predominantly innervated via the locus coeruleus. Clonidine concentration-dependently inhibited K+-evoked norepinephrine release with pIC50 (Imax) of 6.44 ± 0.38 (48.8 ± 6.9%). A selective orexin-1 receptor antagonist, SB-334867 was ineffective. SB-334867 concentration-dependently inhibited orexin A-evoked norepinephrine release with pIC50 (Imax) of 6.05 ± 0.14 (86.4 ± 5.4%); clonidine (α2-agonist) was ineffective. In contrast, yohimbine reversed the inhibitory effects of clonidine (1 μM) on K+-evoked norepinephrine release with pIC50 (Imax) of 6.50 ± 0.34 (77.6 ± 10.9%); orexin A was ineffective. The present data suggest a lack of interaction between orexinergic and α2-adrenergic neurons in rat cerebral cortex.