Nociceptin/orphanin FQ receptors modulate glutamate extracellular levels in the substantia nigra pars reticulata. A microdialysis study in the awake freely moving rat

Intracerebral microdialysis was employed in awake freely moving rats to investigate the effects of nociceptin/orphanin FQ receptor ligands on glutamate extracellular levels in the substantia nigra pars reticulata. Nociceptin/orphanin FQ, ineffective at 0.1 μM, induced a prolonged stimulation of nigral glutamate levels at 1 and 10 μM (mean effect of 137±9 and 167±13%, respectively, of basal values). These effects were prevented by the novel nociceptin/orphanin FQ receptor antagonist [Nphe1]nociceptin/orphanin FQ(1-13)NH2 (100 and 300 μM, respectively) but not by the non-selective opioid receptor antagonist naloxone (10 μM). [Nphe1]nociceptin/orphanin FQ(1-13)NH2 (100 μM) inhibited by itself glutamate outflow (maximal reduction to 71±4%) while naloxone was ineffective. The nociceptin/orphanin FQ receptor ligand [Phe1ψ(CH2-NH)Gly2]nociceptin/orphanin FQ(1-13)NH2 also facilitated glutamate outflow at 10 μM (mean effect of 145±10%). Intranigral perfusion with tetrodotoxin (1 μM) or with the...